We describe a patient with acquired thrombin inhibitor who developed tibial and peroneal neuropathies followed by lumbar plexopathy as a result of large calf and psoas muscle hematomas. Thrombin time, Prothombin time, and partial thromboplastin time were prolonged after repeated exposures to topical bovine thrombin in two orthopedic procedures Specific coagulation tests revealed that the coagulopathy was the result of an inhibitor to bovine thrombin that cross-reacted with human thrombin. We emphasize the risk of spontaneous hematomas that can compromise peripheral nerves as a result of an acquired coagulopathy following bovine thrombin exposure.