Objective: This study reports the results of a prospective, multicenter trial designed to evaluate the safety and effectiveness of the Zenith fenestrated endovascular graft (Cook Medical, Bloomington, Ind) for treatment of juxtarenal abdominal aortic aneurysms (AAAs). Methods: Sixty-seven patients with juxtarenal AAAs were prospectively enrolled in 14 centers in the United States from 2005 to 2012. Custom-made fenestrated stent grafts were designed with one to three fenestrations on the basis of analysis of computed tomography data sets. Renal alignment was performed with balloon-expandable stents. Follow-up included clinical examination, laboratory studies, mesenteric-renal duplex ultrasound, abdominal radiography, and computed tomography imaging at hospital discharge and at 1 month, 6 months, and 12 months and yearly thereafter up to 5 years. Results: There were 54 male and 13 female patients with a mean age of 74 6 8 years enrolled. Mean aneurysm diameter was 60 6 10 mm. A total of 178 visceral arteries required incorporation with small fenestrations in 118, scallops in 51, and large fenestrations in nine. Of these, all 118 small fenestrations (100%), eight of the scallops (16%), and one of the large fenestrations (11%) were aligned by stents. Technical success was 100%. There was one postoperative death within 30 days (1.5%). Mean length of hospital stay was 3.3 ± 2.1 days. No aneurysm ruptures or conversions were noted during a mean follow-up of 37 ± 17 months (range, 3-65 months). Two patients (3%) had migration ≥10 mm with no endoleak, both due to cranial progression of aortic disease. Of a total of 129 renal arteries targeted by a fenestration, there were four (3%) renal artery occlusions and 12 (9%) stenoses. Fifteen patients (22%) required secondary interventions for renal artery stenosis/occlusion in 11 patients, type II endoleak in three patients, and type I endoleak in one patient. At 5 years, patient survival was 91% ± 4%, and freedom from major adverse events was 79% ± 6%; primary and secondary patency of targeted renal arteries was 81% ± 5% and 97% ± 2%, freedom from renal function deterioration was 91% ± 5%, and freedom from secondary interventions was 63% ± 9%. Conclusions: This prospective study demonstrates that endovascular repair of juxtarenal AAAs with the Zenith fenestrated AAA stent graft is safe and effective. Mortality and morbidity are low in properly selected patients treated in centers with experience in these procedures.