Objective: Graft excision and neo-aortoiliac system (NAIS) reconstruction with large caliber, femoral popliteal vein (FPV) grafts have been reported as successful treatment of aortic graft infection (AGI) in several small series with limited follow-up. The goal of this study was to evaluate long-term outcomes in large cohort of consecutive patients treated with NAIS for AGI. Methods: From 1990 to 2006, 187 patients (age: 63 ± 10 years) with AGI were treated with in situ reconstructions using 336 FPV grafts. Data from a prospectively maintained data base were analyzed. Results: NAIS reconstruction was performed for 144 infected aortofemoral bypasses, 21 infected aortic-iliac grafts, and 22 infected axillofemoral bypasses that had been placed to treat AGI. Polymicrobial cultures were present in 37% while 17% showed no growth. There were 55% gram positive, 32% gram negative, 13% anaerobic, and 18% fungal infections. The mean Society for Vascular Surgery run-off resistance score was 4.5 ± 2.3. Concomitant infrainguinal bypass was necessary in 27 (14%) patients (32 limbs). Major amputations were performed in 14 (7.4%) patients. Out of 14 amputations, five patients had irreversible ischemia and in four, there was no conduit available. Graft disruption from reinfection occurred in 10 patients (5%). While 30-day mortality was 10%, procedure-related mortality was 14%. Independent risk factors for perioperative death on multivariate analysis were: preoperative sepsis (odds ratio [OR] 3.5) ASA class 4 (OR 2.9), Candida species (OR 3.4), Candida glabrata (OR 7.6), Klebsiella pneumoniae (OR 3.5), and Bacteroides fragilis (OR 4.1). Perioperative factors included use of platelets (OR 2.4), blood loss >3.0 liters (OR 9.5). Cumulative primary patency at 72 months was 81%; secondary/assisted primary patency was 91%. Limb salvage at 72 months was 89%. Five-year survival was 52%. Conclusions: These results compare favorably with other methods of treating AGI, especially in patients with multilevel occlusive disease. Principle advantages include acceptable perioperative mortality, low amputation rate, superior durability with excellent long-term patency, and freedom from secondary interventions and recurrent infections.