Acquired factor VIII (FVIII) inhibitor induces a bleeding disorder caused by specific antibodies to FVIII. The cause of approximately one fifth of cases can be attributed to autoimmune disorders, such as pemphigus. Here, we describe a case of refractory acquired FVIII inhibitor in a patient with primary pemphigus and its successful treatment with low-dose rituximab. Coagulation studies revealed a prolonged activated partial thromboplastin time, which could not be corrected with the mixing test. At the same time, the FVIII activity level was significantly reduced, and the FVIII inhibitor titer was elevated. A treatment regimen with prednisolone/cyclophosphamide followed by prednisolone/cyclosporine was used. The patient temporarily responded but then became resistant to these medicines. However, subsequent treatment with low-dose rituximab achieved considerable clinical and laboratory improvement in the same patient. Follow-up at 6 months revealed a low level of residual FVIII inhibitor activity with normal coagulation functions. No drug-related side effects were detected. In conclusion, our results indicate that low-dose rituximab might be an effective and safe treatment for patients with acquired FVIII inhibitor.