BACKGROUND: Bleeding associated with warfarin anticoagulation correlates directly to duration and degree of international normalized ratio (INR) elevation above the therapeutic range. Safe and rapid reversal of excessive anticoagulation is occasionally needed to treat or avoid hemorrhagic complications. OBJECTIVE: To evaluate the efficacy and safety of human recombinant factor VIIa (rFVIIa) concentrate in persons requiring rapid reversal of the effects of warfarin. DESIGN: Uncontrolled case series. SETTING: Academic medical center. PATIENTS: 13 patients with critically increased INRs requiring immediate reversal of warfarin-induced anticoagulation. MEASUREMENTS: Prothrombin time and INR were measured before and after administration of varying doses of rFVIIa. RESULTS: Critically prolonged INR and bleeding complications were treated successively and rapidly in all patients, regardless of rFVIIa dose (range, 15 to 90 microg/kg of body weight). Indications for use of rFVIIa included an INR greater than 10 in high-risk persons (n = 5), clinical hemorrhage (n = 4), and diagnostic or therapeutic procedures (n = 4). CONCLUSION: Safe, rapid, and effective administration of rFVIIa corrects critically prolonged INRs and can avert or reverse bleeding associated with warfarin anticoagulation.