S-8

As filed with the Securities and Exchange Commission on May 23, 2005.

Registration No. 333-                    

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-8

REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933

ENCYSIVE PHARMACEUTICALS INC.

(Exact Name of Registrant as Specified in Its Charter)

Delaware
(State or Other Jurisdiction
of Incorporation or Organization) 13-3532643
(I.R.S. Employer
Identification No.)

4848 Loop Central Drive, Suite 700
Houston, Texas 77081
(Address and Zip Code of Principal Executive Offices)

ENCYSIVE PHARMACEUTICALS INC.
AMENDED AND RESTATED 1999 STOCK INCENTIVE PLAN

(Full Title of the Plan)

Name, Address and Telephone	Copy of Communications to:
Number of Agent for Service:
Stephen L. Mueller
Vice President, Finance and Administration, Secretary
and Treasurer	Robert G. Reedy
Encysive Pharmaceuticals Inc.	Porter & Hedges, L.L.P.
4848 Loop Central Drive, Suite 700	1000 Main Street, 36th Floor
Houston, Texas 77081	Houston, Texas 77002-6336
(713) 796-8822	(713) 226-6000

CALCULATION OF REGISTRATION FEE

						Proposed
	Amount to			Proposed Maximum Offering		Maximum Aggregate		Amount of
Title of Each Class of Securities to be Registered	be Registered (1)			Price per Share (2)		Offering Price (2)		Registration Fee
Common Stock, par value $.005 per share		2,000,000	(3)		$10.05		$20,100,000		$2,366

(1)	Pursuant to Rule 416(a), also registered hereunder are an indeterminate number of shares of common stock issuable as a result of the anti-dilution provisions of the Encysive Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan (the “Plan”).
(2)	Pursuant to Rule 457(c), the registration fee is calculated on the basis of the average of the high and low sale prices for the common stock on The Nasdaq Stock Market on May 18, 2005, $10.05. Pursuant to General Instruction E to Form S-8, the registration fee is calculated only with respect to additional securities registered under the Plan.
(3)	Includes one preferred stock purchase right (the “Rights”) for each share of common stock. Pursuant to Rule 457(g) of the Securities Act no separate fee is required for the Rights.

Statement Under General Instruction E — Registration of Additional Securities

      This registration statement registers an additional 2,000,000 shares of our common stock related to the Amended and Restated 1999 Stock Incentive Plan which are the same class as other securities for which registration statements on Form S-8, File No. 333-116178, File No. 333-107941, File No. 333-72468 and File No. 333-79477 (the “Prior Registration Statements”), have been previously filed. Pursuant to General Instruction E of Form S-8, the contents of the Prior Registration Statements are hereby incorporated by reference.

Item 8. Exhibits

Exhibit
No.	Description
4.1	Encysive Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan (incorporated herein by reference to Appendix B of the Proxy Statement on Schedule 14A filed April 7, 2005).
*5.1	Opinion of Porter & Hedges, L.L.P. with respect to the legality of the securities.
*23.1	Consent of Porter & Hedges, L.L.P. (included in Exhibit 5.1).
*23.2	Consent of KPMG LLP.
*24.1	Power of Attorney (included on signature page of this registration statement).

* Filed herewith.

2

SIGNATURES

      Pursuant to the requirements of the Securities Act of 1933, the registrant 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 the city of Houston, state of Texas, on this 23rd day of May, 2005.

ENCYSIVE PHARMACEUTICALS INC.
By:	/s/ Bruce D. Given, M.D.
	Bruce D. Given, M.D.
	President and Chief Executive Officer

POWER OF ATTORNEY

      KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Bruce D. Given, M.D. and Stephen L. Mueller, and each of them, either of whom may act without joinder of the other, his or her true and lawful attorneys-in-fact and agents, with full power of substitution and resubstitution, for him or her and in his or her name, place and stead, in any and all capacities, to sign any or all pre- and post-effective amendments and supplements to this registration statement, and to file the same, or cause to be filed the same, with all exhibits thereto, and other documents in connection therewith, with the Securities and Exchange Commission, granting unto such attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, and each of them, or the substitute or substitutes of either of them, may lawfully do or cause to be done by virtue hereof.

      Pursuant to the provisions of the Securities Act of 1933, this registration statement has been signed by the following persons in the capacities and on the date indicated.

Signature	Title	Date
/s/ John M. Pietruski John M. Pietruski	Chairman of the Board of Directors	May 23, 2005
/s/ Bruce D. Given Bruce D. Given, M.D.	President, Chief Executive Officer and Director (Principal Executive Officer)	May 23, 2005
/s/ Richard A. F. Dixon Richard A. F. Dixon, Ph.D.	Senior Vice President, Research, Chief Scientific Officer and Director	May 23, 2005
/s/ Stephen L. Mueller Stephen L. Mueller	Vice President, Finance and Administration, Secretary and Treasurer (Principal Financial and Accounting Officer)	May 23, 2005
/s/ James T. Willerson James T. Willerson, M.D.	Chairman of the Scientific Advisory Board and Director	May 23, 2005
/s/ Ron J. Anderson Ron J. Anderson, M.D.	Director	May 23, 2005
/s/ J. Kevin Buchi J. Kevin Buchi	Director	May 23, 2005
/s/ Frank C. Carlucci Frank C. Carlucci	Director	May 23, 2005

3

Signature	Title	Date
/s/ Robert J. Cruikshank Robert J. Cruikshank	Director	May 23, 2005
/s/ John H. Dillon John H. Dillon, II	Director	May 23, 2005
/s/ Suzanne Oparil Suzanne Oparil, M.D.	Director	May 23, 2005
/s/ James A. Thomson James A. Thomson, Ph.D.	Director	May 23, 2005

4

INDEX TO EXHIBITS

Exhibit
No.	Description
4.1	Encysive Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan (incorporated herein by reference to Appendix B of the Proxy Statement on Schedule 14A filed April 7, 2005).
*5.1	Opinion of Porter & Hedges, L.L.P. with respect to the legality of the securities.
*23.1	Consent of Porter & Hedges, L.L.P. (included in Exhibit 5.1).
*23.2	Consent of KPMG LLP.
*24.1	Power of Attorney (included on signature page of this registration statement).

* Filed herewith.

5

EX-5.1

Exhibit 5.1

May 23, 2005

Encysive Pharmaceuticals Inc.
4848 Loop Central Drive, Suite 700
Houston, Texas 77081

     Re:       Encysive Pharmaceuticals Inc. Registration Statement on Form S-8; Amended and Restated 1999 Stock Incentive Plan

Gentlemen:

      We have acted as counsel to Encysive Pharmaceuticals Inc., a Delaware corporation (the “Company”), in connection with the preparation for filing with the Securities and Exchange Commission (the “Commission”) of a Registration Statement on Form S-8 (the “Registration Statement”) under the Securities Act of 1933, as amended (the “Securities Act”). The Registration Statement relates to the registration of an additional 2,000,000 shares (the “Shares”) of the Company’s common stock, par value $.005 per share (the “Common Stock”), issuable pursuant to the Company’s Amended and Restated 1999 Stock Incentive Plan (the “Plan”).

      We have examined the Plan and such corporate records, documents, instruments and certificates of the Company, and have reviewed such questions of law as we have deemed necessary, relevant or appropriate to enable us to render the opinion expressed herein. In such examination, we have assumed without independent investigation the authenticity of all documents submitted to us as originals, the genuineness of all signatures, the legal capacity of all natural persons, and the conformity of any documents submitted to us as copies to their respective originals. As to certain questions of fact material to this opinion, we have relied without independent investigation upon statements or certificates of public officials and officers of the Company.

      Based upon such examination and review, we are of the opinion that the Shares have been duly and validly authorized and will, upon issuance and delivery as contemplated by the Plan, be validly issued, fully paid and nonassessable outstanding shares of Common Stock.

      This Firm consents to the filing of this opinion as an exhibit to the Registration Statement. In giving this consent, we do not admit that this Firm is in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations of the Commission promulgated thereunder.

Very truly yours,

/s/ Porter & Hedges, L.L.P.

PORTER & HEDGES, L.L.P.

EX-23.2

Exhibit 23.2

Consent of Independent Registered Public Accounting Firm

The Board of Directors
Encysive Pharmaceuticals Inc.:

We consent to the use of our reports with respect to the consolidated financial statements as of December 31, 2004 and 2003 and for each of the years in the three-year period then ended, management’s assessment of the effectiveness of internal control over financial reporting as of December 31, 2004 and the effectiveness of internal control over financial reporting as of December 31, 2004 incorporated by reference herein.

/s/ KPMG LLP

Houston, Texas
May 19, 2005