Acquired coagulation factor inhibitors are autoantibodies that mainly inhibit the action of coagulation factors, and prompt diagnosis and treatment are important in this situation. Treatment often consists of suppression of hemorrhage, elimination of autoantibodies, and correction of the underlying cause. Therapeutic plasma exchange (TPE) is used as an adjuvant treatment in patients with acquired coagulation factor inhibitors; however, there is no consensus about its clinical significance. Herein, we reported a case of a 70-year-old female patient with acquired coagulation factor inhibitors treated with 13 sessions of TPE after antibiotic treatment. The presence of inhibitors was confirmed by the increased coagulation times without correction in the mixing tests and a factor VIII inhibitor level of 12 Bethesda U/mL. Since the patient could not undergo conventional immunosuppressive therapy because of suspected infective endocarditis and spinal osteomyelitis, only TPE was performed with a successful outcome. To our knowledge, this is the first case where acquired coagulation factor inhibitors were managed by TPE alone. Therefore, TPE might be an effective treatment option in patients with acquired coagulation factor inhibitors when conventional immunosuppressive therapy cannot be applied.