The purpose of this study was to describe the outcome of patients undergoing surgery with recognized and unrecognized factor VIII inhibitor. The setting was a tertiary care center with a community-based general surgery training program. Two patients with acquired factor VIII inhibitor coagulopathy required cholecystectomy. Interventions included intravenous immunoglobulin (IVIG) and factor VIII transfusions. An elderly patient undergoing urgent open cholecystectomy for acute cholecystitis exsanguinated despite postoperative recognition and treatment of factor VIII inhibitor. A second patient with known factor VIII inhibitor underwent laparoscopic cholecystectomy with perioperative transfusions of factor VIII and IVIG. No hemorrhage occurred, but cost to the patient exceeded 50,000 dollars. Acquired factor VIII inhibitor coagulopathy is rare and potentially lethal. Preoperative recognition and appropriate hematologic intervention is crucial to achieve a successful outcome.