BACKGROUND: To report outcomes after the use of the Omniflow II biosynthetic graft (LeMaitre Vascular, Il, United States) for vascular reconstruction in patients with prosthetic infection at the aorto-iliac and femoropopliteal level. METHODS: Within a 6-year period, all consecutive patients with aorto-iliac and femoropopliteal graft infection treated by resection of the infected graft material, extensive local debridement, and reconstruction using Omniflow II biosynthetic graft were retrospectively analyzed. Patient characteristics, intraoperative details, postoperative outcomes, and infection details were assessed. RESULTS: Overall 18 patients were operated in the study period. The anatomical localization of the index surgery was the abdominal aorta n = 3 (17%), iliac arteries n = 5 (27%), and lower extremities (thigh) n = 10 (56%). Previous surgery included 8 (44%) reconstructions with alloplastic and 10 (55.6%) reconstructions with bovine xenopericardium. An obturator rerouting for the aorto-iliac level was used in eight patients (44%), a femorofemoral crossover routing was used in seven patients (39%), and a femoropopliteal routing was used in three patients (17%). Overall, three patients (17%) expired in hospital. Five (28%) patients required secondary wound closure. Operative revision due to bleeding was performed in 3 patients. During follow-up (mean 41.4 ± 25.7 months), 1 patient received a stent angioplasty to maintain graft patency. We observed 1 reinfection (6%), treated by explanation of the prosthesis, and no further revascularization was performed. Secondary graft patency was 100%, and 1 reintervention at the level of the foramen obturatum was needed. CONCLUSIONS: The concept of using the Omniflow II biosynthetic graft for vascular reconstruction in patients with prosthetic infection at the aorto-iliac and femoropopliteal level shows very promising midterm results. Graft patency is high and reinfection rate is low.