The treatment of bleeding episodes and the provision of perioperative hemostasis in patients with hemophilia in whom coagulation factor inhibitors have developed are a major therapeutic challenge because ordinary replacement therapy is usually ineffective. Herein we report the use of recombinant activated factor VII (rFVIIa) in providing successful hemostasis in a patient with hemophilia A and a high-titer inhibitor to factor VIII during a major orthopedic operation. rFVIIa (102 micrograms/kg) was administered intravenously every 2 to 3 hours for a total of 9 days. No excessive bleeding occurred intraoperatively or postoperatively, and no adverse effects attributable to rFVIIa were observed. This surgical procedure probably represented a greater hemostatic challenge than any previously reported operation in which rFVIIa was used. Thus, this article adds considerably to the growing body of literature that suggests the safety and efficacy of rFVIIa in providing perioperative hemostasis and treating severe bleeding episodes in patients with hemophilia and inhibitors refractory to other treatment modalities.