Objective The objective of this study was to report midterm results of an ongoing physician-sponsored investigational device exemption pivotal clinical trial using physician-modified endovascular grafts (PMEGs) for treatment of patients with juxtarenal aortic aneurysms who are deemed unfit for open repair. Methods Data from a nonrandomized, prospective, consecutively enrolling investigational device exemption clinical trial were used. Data collection began on April 1, 2011, and data lock occurred on May 31, 2015, with outcomes analysis through December 31, 2015. Primary safety and efficacy end points were used to measure treatment success. The primary safety end point was defined as the proportion of subjects who experienced a major adverse event within 30 days of the procedure. The primary efficacy end point was the proportion of subjects who achieved treatment success. Treatment success required the following at 12 months: technical success, defined as successful delivery and deployment of a PMEG with preservation of those branch vessels intended to be preserved; and freedom from type I and III endoleak, stent graft migration >10 mm, aortic aneurysm sack enlargement >5 mm, and aortic aneurysm rupture or open conversion. Results During the 50-month study period, 64 patients were enrolled; 60 began the implant procedure and 59 received the PMEG implant. Aneurysm anatomy, operative details, and lengths of stay were recorded and included aneurysm diameter (mean, 65.9 mm; range, 49-104 mm), proximal seal zone length (mean, 40.8 mm; range, 18.9-72.2 mm), graft manufacture time (mean, 55.1 minutes), procedure time (mean, 156.8 minutes), fluoroscopy time (mean, 39.6 minutes), contrast material use (mean, 75.3 mL), estimated blood loss (mean, 213 mL), and length of hospital stay (mean, 4.1 days) with intensive care unit length of stay (mean, 2.2 days). There were 145 fenestrations made for 110 renal arteries and 38 superior mesenteric arteries (SMAs). One patient had an SMA stent placed before the procedure for severe stenosis, and one subject had the SMA stented during the procedure. Renal arteries were stented whenever possible (93%). There were 102 stented renal arteries in 58 patients. There were no open conversions or explantations. Thirty-day mortality was 5.1% (3/59). There were zero type Ia, one type Ib, and two type III endoleaks during follow-up treated with successful reintervention. The overall rate of major adverse events at 30 days was 11.9%. The primary efficacy end points were achieved in 94.1% of patients. Conclusions These midterm results are favorable and verify our early report that endovascular repair with PMEG is safe and effective for managing patients with juxtarenal aortic aneurysms. PMEG has exceptional midterm rates of morbidity, mortality, and endoleak and may outperform standard endovascular aneurysm repair with favorable anatomy. In patients who are poor open surgical candidates who present with symptomatic or ruptured juxtarenal aortic aneurysms, PMEG continues to be an extremely appealing option as reliable off-the-shelf solutions are not widely available. Preoperative planning remains the key ingredient for success with use of these techniques.