The aim of this study was to evaluate early and follow-up results of below-knee bypasses performed using a bioactive heparin-treated expanded polytetrafluoroethylene (ePTFE) graft in diabetic patients with critical limb ischemia (CLI) in a multicenter retrospective registry involving seven Italian vascular centers and to compare them with those obtained in patients operated on with autologous saphenous vein (ASV) in the same centers in the same period of time. Over an 8-year period, ending in 2009, a heparin-bonded prosthetic graft (Propaten Gore-Tex; W. L. Gore & Associates Inc, Flagstaff, Ariz) was implanted in 180 diabetic patients undergoing below-knee revascularization for CLI in seven Italian hospitals (group 1). In the same period in these seven centers, 133 below-knee bypasses with ipsilateral ASV in diabetics with CLI were performed (group 2). Data concerning these interventions were retrospectively collected in a multicenter registry with a dedicated database. Early (<30 days) results were analyzed in terms of graft patency, major amputation rates, and mortality. Follow-up results were analyzed in terms of primary and secondary graft patency, limb salvage, and survival. The interventions consisted of below-knee bypasses in 132 cases in group 1 (73%) and in 45 cases in group 2 (33%; P < .001); 48 patients in group 1 (27%) and 88 patients in group 2 (67%; P < .001) had distal tibial anastomosis. Patients in group 1 had more frequently adjunctive procedures performed at distal anastomotic sites to improve run-off status. Postoperative and long-term medical treatment consisted of single antiplatelet therapy in 93 cases (52%) in group 1 and in 64 cases (48%, P = ns) in group 2, of double antiplatelet therapy in 18 cases (10%) in group 1 and in four cases (3%; P = .05) in group 2 and of oral anticoagulants in 69 patients in group 1 (38%) and in 65 (49%; P = .02) in group 2. Mean duration of follow-up was 28.3 ± 21.4 months; 308 patients (98%) had at least one postoperative clinical and ultrasonographic examination and 228 (72%) reached at least a 1-year follow-up. Estimated 48-month survival rates were 76.6% in group 1 and 72.7% in group 2 (P = > .9, log-rank 0.08). Primary patency rate at 48 months was significantly better in group 2 (63.5%) than in group 1 (46.3%; P = .03, log-rank 4.1). Assisted primary patency rates at 48 months were 47.3% (SE 0.05) in group 1 and 69% (SE 0.05) in group 2 (P = .01, log-rank 6.3). The rates of secondary patency at 48 months were 57.5% in group 1 and 69.6% in group 2 (P = .1, log-rank 2.3); the corresponding values in terms of limb salvage and amputation free-survival rates were 75.4% and 82.4% (P = .3, log-rank 1), and 59.9% and 64.4% (P = .3, log-rank 0.9), respectively. Data from this large, retrospective registry confirmed that the indexed heparin-bonded ePTFE graft provides satisfactory early and midterm results in diabetic patients undergoing surgical treatment of CLI. While autologous saphenous vein maintains its superiority in terms of primary patency, secondary patency rates are not statistically different, even in the presence of a trend for improved secondary patency with vein graft; and also limb salvage rates are comparable.