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As filed with the Securities and Exchange Commission on December 10, 2004

Registration No. 333-119174

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

AMENDMENT NO. 3

TO

FORM S-1

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

Conor Medsystems, Inc.

(Exact Name of Registrant as Specified in Its Charter)

1003 Hamilton Court

Menlo Park, CA 94025

(650) 614-4100

(Address, Including Zip Code, and Telephone Number, Including Area Code, of Registrant’s Principal Executive Offices)

Frank Litvack, M.D.

Chairman and Chief Executive Officer

Conor Medsystems, Inc.

1003 Hamilton Court, Menlo Park, CA 94025, (650) 614-4100

(Name, Address, Including Zip Code, and Telephone Number, Including Area Code, of Agent For Service)

Copies to:

Approximate Date of Commencement of Proposed Sale to the Public:    As soon as practicable after the effective date of this Registration Statement.

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act, check the following box.  ¨

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement number for the same offering.  ¨

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration number of the earlier effective registration statement for the same offering.  ¨

If delivery of the Prospectus is expected to be made pursuant to Rule 434, check the following box.  ¨

The Registrant hereby amends this Registration Statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment that specifically states that this Registration Statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until the Registration Statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine.

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The information in this prospectus is not complete and may be changed. We may not sell these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and it is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

SUBJECT TO COMPLETION, DATED DECEMBER 10, 2004

PROSPECTUS

5,000,000 Shares

Common Stock

$             per share

We are selling 5,000,000 shares of our common stock. We and the selling stockholder named in this prospectus have granted the underwriters an option to purchase up to 750,000 additional shares of common stock to cover over-allotments. We will not receive any proceeds from the sale of shares by the selling stockholder.

This is the initial public offering of our common stock. We currently expect the initial public offering price to be between $11.00 and $13.00 per share. We have applied to have our common stock approved for quotation on the Nasdaq National Market under the symbol “CONR.”

Investing in our common stock involves risks. See “ Risk Factors” beginning on page 8.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The underwriters expect to deliver the shares to purchasers on or about                     , 2004.

Citigroup

A.G. Edwards

                    , 2004

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Through and including                     , 2005 (25 days after the date of this prospectus), all dealers that buy, sell or trade our common stock, whether or not participating in this offering, may be required to deliver a prospectus. This is in addition to the dealers’ obligation to deliver a prospectus when acting as underwriters and with respect to their unsold allotments or subscriptions.

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SUMMARY

After you read the following summary, you should read and consider carefully the more detailed information and financial statements and related notes that we include in this prospectus. If you invest in our common stock, you are assuming a high degree of risk. See “Risk Factors.”

Corporate Overview

We develop innovative controlled vascular drug delivery technologies. We have initially focused on the development of drug eluting stents to treat coronary artery disease, a market that we believe will grow to over $6 billion by 2008. Stents are tubular mesh devices consisting of interconnected metal struts that are inserted inside an artery to act as scaffolding, propping open a narrowed blood vessel. Our stents have been specifically designed for vascular drug delivery, in contrast to currently available drug eluting stents, which are conventional bare metal stents coated with a drug and polymer. A polymer is a substance used to adhere a drug to the surface of a stent and to modulate its release. Our stents incorporate hundreds of small holes, each acting as a reservoir into which we can load a drug-polymer composition. Through our proprietary design, we can better control drug release kinetics, or the rate of drug release over time. Our clinical efforts are currently focused on the development and commercialization of our COSTAR stent, which is a cobalt chromium paclitaxel eluting stent, for the treatment of restenosis, or the re-narrowing of the inner channel of the artery following balloon angioplasty. Balloon angioplasty is a procedure in which an interventional cardiologist uses a catheter to maneuver a balloon to the site of a blocked artery, where the balloon is inflated to create a larger channel for blood flow. While we believe that our stent technology can support a wide range of drugs, our initial clinical efforts have focused on the use of paclitaxel, an anti-proliferative drug. To date, we have conducted clinical trials involving approximately 745 patients using our drug eluting stents, including more than 200 patients with our COSTAR stent. Currently, we have no products available for commercial sale, and, to date, we have not generated any revenue from the sale of products.

We believe that our drug eluting stents offer significant advantages over conventional surface-coated stents. Our stent design enables a wide range of drug release kinetics and also provides greater directional control over the release of the drug, which we believe allows for more targeted treatment within the artery and more efficient use of the therapeutic agent. A highly distinguishing characteristic of our stent is its use of “ductile hinges,” which are designed to ensure that the drug-polymer composition inlayed into the reservoirs is not extruded, fractured or otherwise disrupted during stent expansion. As a result, we are able to use a wider range of polymers and drugs, including water-soluble compounds, as compared to conventional surface-coated stents.

In May 2004, we announced the four-month follow-up data from our PISCES clinical trial, which was designed to evaluate the safety and performance of paclitaxel delivered at different release kinetics and doses using our stainless steel stent for the treatment of restenosis. The initial results from our PISCES trial indicate, for what we believe to be the first time, that drug release kinetics have an effect on treatment outcomes. The two formulations that demonstrated the most favorable clinical outcomes are the focus of our subsequent EuroSTAR and COSTAR I trials, which are designed to evaluate our COSTAR stent for the treatment of restenosis. In September 2004, we announced four-month follow-up data for one of the four formulation groups from the COSTAR I trial. In the first quarter of 2005, we expect to submit an application to a designated Notified Body in the European Community, which is one of the steps we must undertake prior to marketing our COSTAR stent in the European Community. We expect to submit an investigational device exemption application to the FDA in 2005 for our planned U.S. pivotal clinical trial, COSTAR II, evaluating our COSTAR stent compared to a conventional drug eluting stent. We have not yet received any government regulatory approvals necessary to commercialize our COSTAR stent. If our clinical trials proceed on schedule and the outcomes of these clinical trials are favorable, we anticipate receiving regulatory approval for our COSTAR stent in the European

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Community in late 2005 and in the United States in 2007. We could be delayed by adverse clinical results or regulatory complications, and we may never receive marketing approval.

We have entered into agreements with Biotronik AG, Interventional Technologies, Pvt., Ltd., or IVT, and affiliates of St. Jude Medical, Inc. to distribute our COSTAR stent outside of the United States. We intend to launch our COSTAR stent in India in the first half of 2005 pursuant to our distribution agreement with IVT. No regulatory approval is currently required to market our COSTAR stent in India. We expect to pursue commercialization in the United States with our own sales force.

Industry Background

Treatments for Coronary Artery Disease

Coronary artery disease is a progressive, pathological condition that leads to the obstruction of the blood vessels providing blood flow to the heart muscle. Treatments for patients with life-threatening coronary artery disease have advanced dramatically over the last 20 years, from highly invasive, open-chest bypass surgery to minimally invasive balloon angioplasty procedures. We estimate that more than 500,000 balloon angioplasty procedures are performed each year in the United States, with more than one million balloon angioplasties performed each year worldwide. While less invasive and expensive than open-chest bypass surgery, the ultimate clinical effectiveness of balloon angioplasty has been hampered by restenosis.

Evolution of Stents to Address Restenosis

Bare metal stents became widely used in the mid-1990s in combination with balloon angioplasty and quickly became used in the majority of angioplasty procedures. The use of bare metal stents partially addresses restenosis. However, we estimate that restenosis still occurs in approximately 10% to 35% of bare metal stent implantation procedures within six months of treatment, which typically necessitates repeat angioplasty, restenting or bypass surgery. To address this problem, drug eluting stents were developed. We believe that drug eluting stents represent the most advanced and sophisticated treatment currently available to address restenosis. According to published studies, currently marketed drug eluting stents have been shown in clinical trials to reduce the rate of restenosis to less than 10%.

We estimate that the bare metal stent industry accounted for approximately $2.3 billion in product sales in 2001, prior to the introduction of drug eluting stents. We estimate that bare metal stents were used in the majority of the more than one million angioplasty procedures performed worldwide in 2002. The first two marketed drug eluting stents, Johnson & Johnson’s CYPHER^™ stent and Boston Scientific Corporation’s TAXUS^™ Express^2™ stent, only recently gained regulatory approval. Market adoption of drug eluting stents has been rapid, and we believe that drug eluting stents will capture approximately 90% of the stent market within three years. We believe that the drug eluting stent industry will grow to over $6 billion by 2008. In addition to premium pricing of drug eluting stents, we expect that market growth in the drug eluting stent industry will also be driven by growth in the number of angioplasty procedures.

Our Solution

We believe that our stents possess the following key advantages compared to conventional surface-coated drug eluting stents:

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Our Strategy

Our goal is to become a leading innovator in the emerging field of vascular drug delivery through medical devices. Key elements of our strategy include:

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Risk Factors

We are subject to numerous business risks, including those described below and other risks described under “Risk Factors.”

Risks Related to Financial Condition

As of September 30, 2004, we had a deficit accumulated during the development stage of $34.4 million. We have incurred net losses in each year since our inception in 1999, including net losses of $11.0 million for the year ended December 31, 2003 and $15.8 million for the nine months ended September 30, 2004. We expect to continue to incur significant and increasing operating losses for the next several years. We anticipate that in the near term our ability to generate revenues will depend solely on the successful development, regulatory approval and commercialization of our COSTAR stent.

Risks Related to Intellectual Property

There are numerous U.S. and foreign issued patents and pending patent applications owned by third parties with patent claims in areas that are the focus of our product development efforts. We are aware of patents owned by third parties, to which we do not have licenses, that relate to, among other things:

For example, Boston Scientific Corporation owns a series of patents that cover the use of paclitaxel to treat restenosis generally and also to treat restenosis via a stent. In addition, Angiotech Pharmaceuticals, Inc. is the owner or licensee of, and has licensed to Boston Scientific and Cook Incorporated, a number of patents that also cover the use of paclitaxel coated stents to treat angiogenesis and restenosis. Boston Scientific, Guidant Corporation and other third parties also own other patents that may have a material adverse affect on us. We believe that it is highly likely that one or more third parties will assert a patent infringement claim against the manufacture, use or sale of our COSTAR stent based on one or more of these patents. Investors should assume that a lawsuit alleging that we have infringed or are infringing one or more patents controlled by a third party has been filed by a third party at or prior to the time of this offering. In the event a court determines that we infringe any valid claim in a patent held by a third party, we may, among other things:

We believe that it is unlikely that we would be able to obtain a license to any necessary patent rights controlled by companies, like Boston Scientific, against which we would compete directly.

Corporate Information

We were incorporated in 1999 in Delaware. Our principal executive offices are located at 1003 Hamilton Court, Menlo Park, California 94025, and our telephone number is (650) 614-4100. Our website address is http://www.conormed.com. The information contained in, or that can be accessed through, our website is not part of this prospectus. Unless the context indicates otherwise, as used in this prospectus, the terms “Conor Medsystems,” “we,” “us” and “our” refer to Conor Medsystems, Inc., a Delaware corporation, and its subsidiaries. We use Conor Medsystems^™, Conor^™, COSTAR^™ and the Conor Medsystems logo as trademarks in the United States and other countries. All other trademarks and tradenames mentioned in this prospectus are the property of their respective owners.

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The Offering

The number of shares of common stock to be outstanding immediately after this offering as shown above is based on 25,688,068 shares of common stock outstanding as of September 30, 2004. This number excludes:

Except as otherwise indicated, all information in this prospectus assumes:

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Summary Consolidated Financial Data

The following table summarizes our consolidated financial data. The consolidated statements of operations data for the years ended December 31, 2001, 2002 and 2003 are derived from our consolidated audited financial statements included elsewhere in this prospectus. The consolidated statements of operations data for the period from October 25, 1999 (inception) to December 31, 2000 have been derived from our consolidated audited financial statements not included in this prospectus. The consolidated statements of operations data for the nine months ended September 30, 2003 and 2004 and the period from October 25, 1999 (inception) through September 30, 2004 and the balance sheet data as of September 30, 2004 are derived from our consolidated unaudited financial statements which are included elsewhere in this prospectus. You should read this data together with our consolidated financial statements and related notes included elsewhere in this prospectus and the information under “Selected Consolidated Financial Data” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations.”