This study was conducted to evaluate outcomes of fenestrated-branched endovascular aneurysm repair (F-BEVAR) to treat pararenal (PR) and thoracoabdominal (TAAA) aneurysms performed in high-risk patients and to identify those patients likely to benefit from this treatment. We performed a prospective single-center study of patients treated electively for PR and TAAA repair using F-BEVAR between 2005 and 2016. Survival was estimated with the Kaplan-Meier method. The risk factors associated with 30-day mortality and mortality during follow-up were determined using multivariate statistical techniques with a Cox regression model including all variables that were significant on univariate analysis (P < .05). We analyzed the data from 468 patients (median age, 71.6 years) with American Society for Anesthesiology score of III or IV. There were 221 (47.2%) type 1 to 3 TAAAs and 247 (52.8%) type 4 and PR aneurysms, with a median diameter of 60 mm. Technical success of target vessel stenting was 98.7 % (1497 of 1516). The 30-day mortality rate was 4.9% (23 patients). The spinal cord ischaemia rate was 3.8% (18 patients). Twenty patients (4.3%) required postoperative dialysis, and four (0.8%) required long-term dialysis after discharge. Median follow-up was 29 months. Survival at 1, 3, and 5 years was 86.7% (95% confidence interval [CI], 83.7-89.7), 73.4% (95% CI, 68.4-78.4), and 59.6% (95% CI, 53.6-65.6), respectively. Freedom from target vessel occlusion and from secondary procedures was 94.3% (95% CI, 92.3-96.3) and 88.2% (95% CI, 85.2-91.2) at 1 year, and 88.9% (95% CI, 84.9-92.4) and 70.2% (95% CI, 64.2-76.2) at 5 years, respectively. In multivariate analysis, early mortality was associated with procedure time (hazard ratio [HR], 1.007 per minute; 95% CI, 1.003-1.010; P < .001), TAAA preoperative diameter (HR, 1.053 per mm; 95% CI, 1.020-1.087; P = .001), and chronic kidney disease (HR, 3.139; 95% CI, 1.369-7.196; P = .007). Mortality during follow-up was associated with Crawford type I to III (HR, 1.683; 95% CI, 1.157-2.447; P = .006) as compared with infra diaphragmatic repairs, chronic kidney disease (HR, 1.654; 95% CI, 1.130-2.442, P = .010), TAAA preoperative diameter (HR, 1.025 per mm; 95% CI, 1.008-1.042; P = .004), and age at repair (HR = 1.030 per year; 95% CI, 1.006-1.056; P = .016). F-BEVAR performed in high risk patients is associated with favorable outcomes. Patient selection should take into account the reported risk factors associated with mortality.