When polytetrafluoroethylene (PTFE) must be used for below-knee bypass to achieve limb salvage, effective anticoagulation with warfarin may improve graft survival. We analyzed our practice of routinely using oral anticoagulation to improve graft patency rates for PTFE grafts to below-knee popliteal and crural vessels in limb salvage procedures. We reviewed our established vascular database from February 1999 through April 2003 to identify those patients who required below-knee and tibial artery bypass with PTFE for critical limb ischemia. All patients were initiated on warfarin anticoagulation postoperatively, with an international normalized ratio (INR) of 2.0-3.0 considered therapeutic. All patients were discharged in the therapeutic range. Life-table analysis and Kaplan-Meier estimates were used to compare primary patency rates with regard to INR and position of distal anastomosis. Cox proportional hazards analysis was performed to compare the patency rates for grafts with therapeutic versus subtherapeutic anticoagulation while correcting for variability in distal runoff. Between February 1999 and April 2003, 74 patients (mean age, 69.2 years; 58% men) had 77 below-knee PTFE bypasses. Indications for operation included rest pain (43), ischemic ulcer (27), and gangrene (7). Patients presenting with occluded grafts more often had a subtherapeutic INR. Patients with a subtherapeutic INR (< or = 1.9) had a median primary graft patency of 6.8 months and those with a therapeutic INR (> or = 2.0) had a median primary graft patency of 29.9 months (p = 0.0007). Analysis by Cox proportional hazards model demonstrated a significantly better graft patency rate in patients with a therapeutic INR regardless of outflow vessel. The patency rates of PTFE grafts to infrageniculate vessels may be improved by effective anticoagulation with warfarin. This improved patency rate may also result in improved limb salvage and further support the use of PTFE grafts for critical limb ischemia when autogenous vein is not available. Predictably, the best results are seen with an INR therapeutic range of 2.0 to 3.0.