As filed with the Securities and Exchange Commission on March 1, 2010

Registration No. 333-______

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-8

REGISTRATION STATEMENT UNDER

THE SECURITIES ACT OF 1933

SHIRE PLC

(Exact Name of Registrant as Specified in its Charter)

Jersey (Channel Islands)		98-0601486
(State or Other Jurisdiction of Incorporation or Organization)		(I.R.S. Employer Identification No.)
	5 Riverwalk, Citywest Business Campus, Dublin 24 Republic of Ireland
(Address of Principal Executive Offices)

THE SHIRE EXECUTIVE ANNUAL INCENTIVE PLAN

(Full Titles of the Plan(s))

Scott Applebaum

Senior Vice President and U.S. Associate General Counsel

Shire Pharmaceuticals

725 Chesterbrook Boulevard

Wayne, Pennsylvania 19087

(Name and Address of Agent for Service)

(484) 595-8800

(Telephone Number, Including Area Code, of Agent for Service)

With copies to:
John B. Meade, Esq. Davis Polk & Wardwell LLP 99 Gresham Street London EC2V 7NG +44-20-7418-1011		Kyoko Takahashi Lin, Esq. Davis Polk & Wardwell LLP 450 Lexington Avenue New York, NY 10017 (212) 450-4000

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer x	Accelerated filer o

Non-accelerated filer o (Do not check if a smaller reporting company)	Smaller reporting company o

CALCULATION OF REGISTRATION FEE

Title of Each Class of Securities to be Registered	Amount to Be Registered (2)	Proposed Maximum Offering Price Per Share	Proposed Maximum Aggregate Offering Price	Amount of Registration Fee (5)
Ordinary Shares, nominal value £0.05 per Ordinary Share (“Ordinary Shares”)	300,000	$21.05 (3)	$6,315,000 (3)	$450.26
American Depositary Receipts (“ADRs”) evidencing American Depositary Shares, each American Depositary Share representing three Ordinary Shares, nominal value £0.05 per Ordinary Share (1)	300,000	$63.20 (4)	$18,960,000 (4)	$1,351.85
Total			$25,275,000	$1,802.11

(1)

ADRs evidencing American Depositary Shares deliverable on deposit of the Ordinary Shares of Shire plc (the “Company” or the “Registrant”) have been registered pursuant to a separate Registration Statement on Form F-6 (Registration No. 333-150923) filed with the Securities and Exchange Commission (the “Commission”). Each American Depositary Share represents three Ordinary Shares.

(2)

This Registration Statement on Form S-8 (this “Registration Statement”) covers the estimated maximum aggregate number of Ordinary Shares and/or ADRs (i) issuable pursuant to the Shire Executive Annual Incentive Plan, (ii) to be issued n the future under the Plan (the “Plan”) and (iii) pursuant to Rule 416(a) under the Securities Act of 1933, as amended (the “Securities Act”), any additional Ordinary Shares and/or ADRs that become issuable under the Plan by reason of any stock dividend, stock split, or other similar transaction.

(3)

Estimated pursuant to Rule 457(h) and Rule 457(c) under the Securities Act, solely for the purpose of computing the registration fee, based on the average of the high and low prices reported for an Ordinary Share on the London Stock Exchange on February 24, 2010 (£13.665), converted from Pounds Sterling to U.S. Dollars at the currency cross rate at the close of the NASDAQ Stock Exchange on February 24, 2010, as reported by the Wall Street Journal (£1=U.S.$1.5398). The proposed maximum offering price per share is rounded up to the nearest cent.

(4)	Estimated pursuant to Rule 457(h) and Rule 457(c) under the Securities Act, solely for the purpose of computing the registration fee, based on the average of the high and low prices reported for an ADR on the NASDAQ Exchange on February 24, 2010.

(5)	Rounded up to the nearest cent.

PART I

The information specified in Item 1 and Item 2 of Part I of Form S-8 is omitted from this filing in accordance with the provisions of Rule 428 under the Securities Act and the introductory note to Part I of the Form S-8 instructions. The documents containing the information specified in Part I will be delivered to the participants in the Plan as required by Rule 428(b)(1).

PART II

INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 3. Incorporation of Documents by Reference.

The following documents are incorporated herein by reference:

(a) The Registrant’s Amended Memorandum and Articles of Association as adopted by special resolution passed on April 10, 2008 and amended by special resolution on September 24, 2008, incorporated by reference to Exhibit 99.02 to the Company’s Current Report on Form 8-K, filed on October 1, 2008.

(b) The description of the Company’s Ordinary Shares and ADRs evidencing American Depositary Shares which is contained in the Company’s Current Report on Form 8-K, filed on May 23, 2008, including any amendments or supplements thereto.

(d) All reports filed by the Company pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), since December 31, 2009.

In addition, all documents subsequently filed by the Company pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act prior to the filing of a post-effective amendment to this Registration Statement which indicates that all securities offered have been sold or which deregisters all securities then remaining unsold, shall be deemed to be incorporated by reference in this Registration Statement and to be a part hereof from the date of the filing of such documents.

Any statement contained in a document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded for purposes of this Registration Statement to the extent that a statement contained herein, (or in any other subsequently filed document which also is incorporated or deemed to be incorporated by reference herein), modifies or supersedes such statement. Any such statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this Registration Statement.

Item 4. Description of Securities.

Not applicable.

Item 5. Interests of Named Experts and Counsel.

None.

Item 6. Indemnification of Directors and Officers.

Except as hereinafter set forth, there is no charter provision, by-law, contract, arrangement or statute under which any director or officer of the Registrant is insured or indemnified in any manner against any liability which he may incur in his capacity as such.

Pursuant to Article 155 of the Articles of Association of the Registrant, the Company may indemnify any director of the Company out of the assets of the Registrant for any liability for which the Company may lawfully indemnify that director.

The Company’s Articles of Association provide in relevant part:

“Article 155. Indemnity of Directors

Subject to the provisions of the Companies Laws, the Company may indemnify any director of the Company or of any subsidiary against any liability and may purchase and maintain for any director of the Company or of any subsidiary insurance against any liability. No director of the Company or of any subsidiary shall be accountable to the Company or to the members for any benefit provided pursuant to this article and the receipt of any such benefit shall not disqualify any person from being or becoming a director of the Company.”

The relevant provision of the Companies (Jersey) Law 1991 is Article 77, which provides:

“(1) Subject to paragraphs (2) and (3), any provision, whether contained in the articles of, or in a contract with, a company or otherwise, whereby the company or any of its subsidiaries or any other person, for some benefit conferred or detriment suffered directly or indirectly by the company, agrees to exempt any person from, or indemnify any person against, any liability which by law would otherwise attach to the person by reason of the fact that the person is or was an officer of the company shall be void.

(2) Paragraph (1) does not apply to a provision for exempting a person from or indemnifying the person against –

(a) any liabilities incurred in defending any proceedings (whether civil or criminal) –

(i) in which judgment is given in the person’s favour or the person is acquitted,

(ii) which are discontinued otherwise than for some benefit conferred by the person or on the person’s behalf or some detriment suffered by the person, or

(iii) which are settled on terms which include such benefit or detriment and, in the opinion of a majority of the directors of the company (excluding any director who conferred such benefit or on whose behalf such benefit was conferred or who suffered such detriment), the person was substantially successful on the merits in the person’s resistance to the proceedings;

(b) any liability incurred otherwise than to the company if the person acted in good faith with a view to the best interests of the company;

(c) any liability incurred in connection with an application made under Article 212 in which relief is granted to the person by the court; or

(d) any liability against which the company normally maintains insurance for persons other than directors.

(3) Nothing in this Article shall deprive a person of any exemption or indemnity to which the person was lawfully entitled in respect of anything done or omitted by the person before the coming into force of this Article.

(4) This Article does not prevent a company from purchasing and maintaining for any such officer insurance against any such liability.”

The Company maintains an insurance policy for its directors and officers in respect of liabilities arising out of any act, error or omission while acting in their capacities as directors or officers of the Company or its affiliated companies.

The Company has entered into separate indemnity agreements with each of its current directors to indemnify the director as specified in the applicable indemnity agreement, which may provide for indemnification up to the full

extent permitted by the Companies (Jersey) Law 1991, and will enter into a separate indemnity agreement with any new director.

Item 7. Exemption from Registration Claimed.

Not applicable.

Item 8. Exhibits.

Exhibit Number
4.1		Amended Memorandum and Articles of Association as adopted by special resolution passed on April 10, 2008 and amended by special resolution on September 24, 2008, incorporated by reference to Exhibit 99.02 to the Company’s Current Report on Form 8-K, filed on October 1, 2008.

4.2		Form of Deposit Agreement among Shire plc, JPMorgan Chase Bank, N.A. as depositary and all holders from time to time of ADRs issued thereunder dated November 21, 2005, incorporated by reference to Exhibit 4.02 to Shire’s Form 8-K filed on May 23, 2008.

5		Opinion of Mourant du Feu & Jeune.

23.1		Consent of Deloitte LLP, independent auditors.

23.2		Consent of Mourant du Feu & Jeune (included in Exhibit 5).

24		Power of Attorney (included in the signature pages hereof).

99.1		The Shire Executive Annual Incentive Plan.

Item 9. Undertakings.

(a) The undersigned Registrant hereby undertakes:

(1) To file, during any period in which offers or sales are being made, a post-effective amendment to this Registration Statement:

(i) To include any prospectus required by Section 10(a)(3) of the Securities Act;

(ii) To reflect in the prospectus any facts or events arising after the effective date of this Registration Statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in this Registration Statement;

(iii) To include any material information with respect to the Plan not previously disclosed in this Registration Statement or any material change to such information in this Registration Statement;

provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in periodic reports filed by the Registrant pursuant to Section 13 or 15(d) of the Exchange Act that are incorporated by reference in this Registration Statement.

(2) That, for the purpose of determining any liability under the Securities Act, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

(3) To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

(b) The undersigned Registrant hereby undertakes that, for purposes of determining any liability under the Securities Act, each filing of the Registrant’s annual report pursuant to Section 13(a) or 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit plan’s annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by reference in this Registration Statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

(c) Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers and controlling persons of the Registrant pursuant to the foregoing provisions, or otherwise, the Registrant has been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the Registrant of expenses incurred or paid by a director, officer or controlling person of the Registrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the Registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant, Shire plc, certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in Tilford, Surrey, United Kingdom, on the 26th day of February, 2010.

SHIRE PLC


By:	/s/ Angus Russell
	Name: Angus Russell Title: Chief Executive Officer

POWER OF ATTORNEY

Know all persons by these presents, that each person whose signature appears below, constitutes and appoints each of Angus Russell and Graham Hetherington as his or her true and lawful attorney-in-fact and agent, upon the action of such appointee, with full power of substitution and resubstitution, to do any and all acts and things and execute, in the name of the undersigned, any and all instruments which each of said attorneys-in-fact and agents may deem necessary or advisable in order to enable Shire plc to comply with the Securities Act of 1933, as amended (the “Securities Act”), and any requirements of the Securities and Exchange Commission (the “Commission”) in respect thereof, in connection with the filing with the Commission of this Registration Statement under the Securities Act, including specifically but without limitation, power and authority to sign the name of the undersigned to such Registration Statement, and any amendments to such Registration Statement (including post-effective amendments), and to file the same with all exhibits thereto and other documents in connection therewith, with the Commission, to sign any and all applications, registration statements, notices or other documents necessary or advisable to comply with applicable state securities laws, and to file the same, together with other documents in connection therewith with the appropriate state securities authorities, granting unto each of said attorneys-in-fact and agents full power and authority to do and to perform each and every act and thing requisite or necessary to be done in and about the premises, as fully and to all intents and purposes as the undersigned might or could do in person, hereby ratifying and confirming all that each of said attorneys-in-fact and agents may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement has been signed this 26th day of February, 2010 by the following persons in the following capacities.

Signature	Title	Date

/s/ Angus Russell Angus Russell	Chief Executive Officer and Director (Principal Executive Officer)	February 26, 2010

/s/ Graham Hetherington Graham Hetherington	Chief Financial Officer and Director (Principal Financial Officer and Principal Accounting Officer)	February 26, 2010

______________________ Matthew Emmens	Chairman and Non-Executive Director	____________

/s/ David Kappler David Kappler	Deputy Chairman and Senior Independent Non-Executive Director	February 26, 2010

/s/ Patrick Langlois Patrick Langlois	Non-Executive Director	February 26, 2010

______________________ Dr. Jeffrey Leiden	Vice Chairman and Non-Executive Director	____________

______________________ David Stout	Non-Executive Director	____________

/s/ Kate Nealon Kate Nealon	Non-Executive Director	February 26, 2010

EXHIBIT INDEX

Exhibit Number
4.1		Amended Memorandum and Articles of Association as adopted by special resolution passed on April 10, 2008 and amended by special resolution on September 24, 2008, incorporated by reference to Exhibit 99.02 to the Company’s Current Report on Form 8-K, filed on October 1, 2008.

4.2		Form of Deposit Agreement among Shire plc, JPMorgan Chase Bank, N.A. as depositary and all holders from time to time of ADRs issued thereunder dated November 21, 2005, incorporated by reference to Exhibit 4.02 to Shire’s Form 8-K filed on May 23, 2008.

5		Opinion of Mourant du Feu & Jeune.

23.1		Consent of Deloitte LLP, independent auditors.

23.2		Consent of Mourant du Feu & Jeune (included in Exhibit 5).

24		Power of Attorney (included in the signature pages hereof).

99.1		The Shire Executive Annual Incentive Plan.