Topical hemostatic products containing thrombin are commonly used in burn surgery to facilitate focal hemostasis and graft adherence. Until recently, thrombin was available only from a bovine source, which has been documented to produce antibodies to endogenous clotting factors and to induce coagulation defects and severe bleeding complications. This report documents the first case of factor V deficiency and profound coagulopathy in a burn patient after intraoperative exposure to bovine thrombin. A 38-year-old woman was admitted after a 75% total body surface area burn. The patient underwent repeated excision and grafting during which an epinephrine solution that contained bovine thrombin was used to facilitate hemostasis. During the fourth and subsequent operative procedures, the patient developed profound coagulopathy as evidenced by excessive bleeding and abnormal laboratory coagulation parameters, requiring the administration of supplemental clotting factors through fresh frozen plasma and cryoprecipitate. Hematology work-up revealed a factor V deficiency. Subsequent procedures in which bovine thrombin was avoided were uneventful. The use of topical bovine thrombin in patients who have been previously exposed results in an increased risk of perioperative coagulopathy and clinically significant bleeding complications. Thus, the use of bovine-thrombin-containing products should be avoided in burn patients with prior exposure to bovine thrombin.