OBJECTIVE Long-term results of precuffed expanded polytetrafluoroethylene (ePTFE) grafts used for peripheral bypass surgery are lacking. The aim of this study was to obtain the long-term outcomes of precuffed ePTFE grafts compared with autologous saphenous vein (ASV) grafts used in patients with peripheral arterial disease (PAD). METHODS A single-institution retrospective study of precuffed ePTFE and ASV graft performances in patients with PAD was undertaken between January 2004 and December 2012. Five-year primary patency, secondary patency, and limb salvage rates were determined by Kaplan-Meier analyses. RESULTS A total of 467 bypass grafts were included in this study (169 precuffed ePTFE grafts and 298 ASV grafts). Secondary patency rates of ePTFE vs ASV at 1 and 5 years, respectively, were as follows: for 134 supragenicular femoropopliteal bypasses, 60% and 27% vs 89% and 85% (P < .05); for 190 infragenicular femoropopliteal bypasses, 40% and 25% vs 86% and 79% (P < .05); and for 84 femorocrural bypasses, 30% and 14% vs 50% and 50% (P < .05). Five-year limb salvage rates of ePTFE vs ASV for supragenicular femoropopliteal bypasses were 82% vs 94% (P = .16); for infragenicular femoropopliteal bypasses, 41% vs 92% (P < .05); and for femorocrural bypasses, 43% vs 64% (P = .06). CONCLUSIONS ASV bypasses are still the first-choice conduit in peripheral bypass surgery performed in patients with PAD. Precuffed ePTFE bypasses are acceptable alternatives in the absence of adequate autologous vein.