Acquired autoantibodies to factor VIII in patients without hemophilia are rare, but they cause severe illness and death if not eradicated. To examine daily therapy with oral cyclophosphamide and prednisone for acquired hemophilia. Case series. Academic medical center. Nine consecutive patients without hemophilia who had severe hemorrhage caused by high titers of factor VIII inhibitors. Daily oral cyclophosphamide and prednisone. Coagulation factors were used only for bleeding. Plasma titers of factor VIII inhibitor, factor VIII activity, and clinical evidence of bleeding. All patients achieved complete remission, which was defined as loss of residual inhibitor activity and return to a normal titer of factor VIII. Therapy lasted a median of 12 weeks (range, 3 to 37 weeks). Bleeding resolved in a median of 3 weeks (range, 2 to 10 weeks). Median follow-up after discontinuation of therapy was 91 weeks (range, 61 to 164 weeks). Daily administration of oral cyclophosphamide and prednisone without empirical factor VIII therapy seems to be an effective and well-tolerated treatment for acquired hemophilia.