The aim of the study was to evaluate the immediate and long-term results of femoropopliteal bypasses performed with a new bioactive heparin-treated expanded polytetrafluoroethylene (ePTFE) graft in a single-center experience. From March 2002 to April 2006, 51 patients underwent lower limb revascularization with a new bioactive ePTFE prosthetic graft with covalent end-point attachment of heparin to the graft surface. Data concerning preoperative assessment, intraoperative strategy, drug administration, and follow-up surveillance program were prospectively collected in a dedicated database; early results were analyzed in terms of graft patency, amputation rate, and deaths. Follow-up consisted of clinical and duplex scan examination at 1, 6, and 12 months and yearly thereafter. Midterm results in terms of primary and secondary patency, limb salvage, and survival were analyzed. Patients were predominantly male (35 patients, 71%), with a mean age of 71 years (SD = 9.05). Indications for surgical revascularization were critical limb ischemia in 36 patients and severe intermittent claudication in 15 patients. Interventions were performed for occlusion of a native vessel in 35 cases, whereas 12 patients had late thrombosis of a femoropopliteal bypass; the remaining four patients were operated on for an occluded popliteal artery aneurysm. Intervention consisted of below-knee bypass in 34 patients, while the other 17 had an above-knee revascularization. No perioperative deaths occurred. Cumulative 30-day graft patency was 88%, with an amputation rate of 4% (two cases). Results were similar in above- and below-knee revascularizatons. Mean duration of follow-up was 18 months (SD = 7). Cumulative estimated 24-month survival and primary patency rates were 97% and 80.2%, respectively; the corresponding limb salvage rate was 85.7%. Long-term results did not significantly differ in above- and below-knee revascularizatons. In our experience, the use of a modified ePTFE graft with covalent end-point linkage of heparin molecules on the graft surface provides good early and midterm results, with low rates of graft thrombosis and amputation.