This report describes a case of severe coagulopathy and bleeding related to the intraoperative use of topically applied thrombin. Commercial thrombin preparations contaminated with bovine factor V have been shown to stimulate the production of antibodies directed against factor V. These antibodies can cause coagulopathy. Our patient developed antibodies against factor V after intraoperative exposure to topical thrombin. The resulting antibody-mediated depletion of factor V caused a severe and refractory coagulopathy. Vascular surgeons should be aware that the use of topical bovine thrombin can cause severe coagulopathy.