BACKGROUND: Postpartum hemorrhage may be a life-threatening event and may result from coagulation defects. CASE: We report a case of a multigravida woman who developed rapidly progressive postpartum bleeding as a result of acquired factor VIII inhibitors. Repeated laparotomies and massive transfusions failed to achieve adequate control of bleeding. Laboratory studies revealed a prolonged activated partial thromboplastin time, and the presence of specific inhibitors was soon established. The patient responded only partially to steroids and immunotherapy. Upon administration of rituximab, an anti-CD-20 monoclonal antibody, control of bleeding was achieved. CONCLUSION: Early diagnosis of acquired hemophilia as a rare cause of postpartum hemorrhage is crucial, because specific therapy may be life saving.