Orthopedic patients are at a high risk for developing venous thromboembolism, yet only a fraction of eligible patients receive anticoagulation prophylaxis after hospital discharge. This pilot study compared the efficacy of a fixed 2 mg/d dose of warfarin versus an adjusted higher dose of warfarin for 1 month after discharge to prevent the development of proximal leg deep venous thrombosis among recently discharged orthopedic patients. After standard inhospital treatment with adjusted higher-dose warfarin and a predischarge leg ultrasound to exclude deep venous thrombosis, 96 orthopedic patients were randomized just prior to discharge to either fixed low-dose (n = 49) or adjusted higher-dose warfarin (n = 47). At the 6-week follow-up evaluation, ultrasonographically confirmed, asymptomatic, proximal leg deep venous thrombosis occurred in two patients (4%). Both patients were randomized to the fixed low-dose group, although one remained on adjusted higher-dose warfarin throughout the trial. No patient in either group developed major bleeding complications. Further studies should be undertaken to further test fixed low-dose warfarin for venous thromboembolic prevention in high-risk orthopedic patients.