BACKGROUND: This study prospectively analyzed the midterm results of above-the-knee femoropopliteal bypass (AKb) using bioactive heparin-bonded expanded polytetrafluoroethylene (HB-ePTFE) graft in patients with femoropopliteal occlusive disease.Methods and Results:This prospective, multicenter, non-randomized study reviewed limbs undergoing AKb with HB-ePTFE graft for femoropopliteal lesion in 20 Japanese institutions between July 2014 and October 2017. Primary efficacy endpoints were primary, primary assisted, and secondary graft patency. Safety endpoints included any major adverse limb event and perioperative mortality. During the study period, 120 limbs of 113 patients (mean age, 72.7 years) underwent AKb with HB-ePTFE grafts. A total of 45 patients (37.5%) had critical limb ischemia and 17 (15.0%) were on hemodialysis (HD). Median duration of follow-up was 16 months (range, 1-36 months). Estimated 1- and 2-year primary, primary assisted, and secondary graft patency rates were 89.4% and 82.7%, 89.4% and 87.2%, and 94.7% and 92.5%, respectively. On univariate analysis of 2-year primary graft patency, having 3 run-off vessels, cuffed distal anastomoses, no coronary artery disease, and no chronic kidney disease requiring HD were significantly associated with favorable patency. CONCLUSIONS: AKb using HB-ePTFE grafts achieved favorable 2-year graft patency. AKb using HB-ePTFE grafts may therefore be an acceptable, highly effective treatment option for femoropopliteal artery lesions.