To determine systemic and local risk factors that contribute to limb loss despite a patent infra-inguinal bypass graft and how to prevent it, we reviewed 987 patients who underwent infra-inguinal bypasses at our institution. Seventy-five (7.6%) patent grafts failed to achieve a healed foot despite exhaustive attempts to do so and these patients underwent major amputation either above the knee (AKA) or below the knee (BKA). In 525 femoro-popliteal bypasses, there were 38 major amputations (29 BKA; 9 AKA) with a patent graft; in 462 femoro-distal bypasses, there were 37 amputations (22 BKA; 15 AKA) with a patent graft. The remaining 912 patients with limb salvage as well as all the patients with limb loss were evaluated with regard to systemic risk factors, quality of the run-off from the popliteal artery, continuity of the tibial artery into the arch as demonstrated on arteriography, the haemodynamic improvement obtained postoperatively, and the presence and extent of necrosis in the foot. The presence of diabetes, extensive pedal necrosis and advanced infection predispose to limb loss despite a patent lower extremity bypass graft. Patients who lost their limbs despite a functioning bypass to an isolated popliteal segment had significantly less pronounced haemodynamic improvement postoperatively. An early graft extension to a reconstituted tibial or peroneal artery or a direct bypass to a distal tibial or peroneal artery may reduce the incidence of limb loss in this setting. When a patent bypass to an isolated tibial or peroneal artery segment failed to relieve foot ischaemia, limb salvage was achieved by a distal extension to plantar arteries.