© 2019 Society for Vascular Surgery Objective: Open repair of extent II and III thoracoabdominal aortic aneurysms (TAAA) is associated with substantial morbidity. Alternative strategies, such as hybrid operations combining proximal thoracic endovascular aortic repair with either staged open distal TAAA repair or visceral debranching (hybrid), as well as fenestrated/branched endografts (FEVAR), have been increasingly reported; however, benefits of these approaches compared with direct open surgery remain unclear. The purpose of this study was to compare outcomes of these three different strategies in the management of extent II/III TAAA. Methods: All extent II/III TAAA repairs (2002-2018) for nonmycotic, degenerative aneurysm or chronic dissection at a single institution were reviewed. The primary end point was 30-day mortality. Secondary end points included incidence of spinal cord ischemia (SCI), complications, unplanned re-operation, 90-day readmission, and out-of-hospital survival. To mitigate impact of covariate imbalance and selection bias, intergroup comparisons were made using inverse probability weighted-propensity analysis. Cox regression was used to estimate survival while cumulative incidence was used to determine reoperation risk. Results: One hundred ninety-eight patients (FEVAR, 92; hybrid, 40; open, 66) underwent repair. In unadjusted analysis, compared with hybrid/open patients, FEVAR patients were significantly older with more cardiovascular risk factors, but less likely to have a connective tissue disorder or dissection-related indication. Unadjusted 30-day mortality and complication rates were: 30-day mortality, FEVAR 4%, hybrid 13%, open 12% (P =.01); and complications, FEVAR 36%, hybrid 33%, open 50% (P =.11). Permanent SCI was not different among groups (FEVAR 3%, hybrid 3%, open 6%; P =.64). In adjusted analysis, 30-day mortality risk was greater for open vs FEVAR (hazard ratio, 3.6; 95% confidence interval, 1.4-9.2; P =.01) with no difference for hybrid vs open/FEVAR. There was significantly lower risk of any SCI for open vs FEVAR (hazard ratio, 0.3; 95% confidence interval, 0.09-0.96; P =.04); however, no difference in risk of permanent SCI was detected among the three groups. There was no difference in complications or unplanned reoperation, but open patients had the greatest risk of unplanned 90-day readmission. There was a time-varying effect on survival probability, with open repair having a significant survival disadvantage in the first 1 to 6 months after the procedure compared with hybrid/FEVAR patients (Cox model P =.03), but no difference in survival at 1 and 5 years (1- and 5-year survival: FEVAR, 86 ± 3%, 55 ± 8%; hybrid, 86 ± 5%, 60 ± 11%; open 69 ± 7%, 59 ± 8%; Cox-model P =.10). Conclusions: Extent II/III TAAA repair, regardless of operative strategy, is associated with significant morbidity risk. FEVAR is associated with the lowest 30-day mortality risk compared with hybrid and open repair when estimates are adjusted for preoperative risk factors. These data support greater adoption of FEVAR as first-line therapy to treat complex TAAA disease in anatomically suitable patients who present electively.