Purpose: The purpose of this study was to evaluate the merit of polytetrafluoroethylene (PTFE) extensions and interpositions for the management of failing infrainguinal vein bypass grafts. Methods: The treatment of 133 failing vein grafts in 125 patients over a 10-year period was retrospectively reviewed. Twenty-two graft-threatening lesions were detected in patients who did not have a usable autogenous vein conduit as determined by preoperative and intraoperative evaluations. A PTFE extension or interposition graft was used for the necessary reconstruction in all cases. Results: Ten lesions were within the vein graft, 11 were proximal to the graft in the femoral or popliteal artery segments, and one was distal to the graft in the popliteal artery. The treatment of these lesions included 19 extensions and three mid graft interpositions. The vein graft lesions developed significantly sooner (mean 10.6 ± 2.5 months) after the bypass (p < 0.05) than the arterial lesions (mean 28.0 ± 6.1 months). The 3-year cumulative secondary patency rate for these vein grafts treated with PTFE extensions or interpositions was 84% ± 8%. This was not significantly different from the 3-year cumulative secondary patency rate for vein grafts treated with vein extensions or interpositions at our institution over the same time period (82% ± 10%). The 3-year limb salvage rates were 95% and 89%, respectively. Conclusions: These results indicate that PTFE extensions and interpositions can be used successfully to maintain the patency of failing vein grafts and may serve to prolong limb salvage in patients without any usable autogenous vein. Early reintervention with a PTFE conduit in this difficult group of patients is appropriate to salvage a failing vein graft.