Background: An increased degree of aortic angulation (AA) represents a challenging feature for bioprosthesis positioning. Whether AA has an impact on procedural outcomes of contemporary self-expanding valves remains unsettled. The aim of this study was to evaluate the impact of AA on procedural outcomes of transcatheter aortic valve replacement with contemporary self-expanding valves. Methods: The HORSE (Horizontal Aorta in Transcatheter Self-Expanding Valves) is an international, retrospective registry including 3862 consecutive patients undergoing transcatheter aortic valve replacement with either Evolut R/PRO (n=1959) or ACURATE neo (n=1903) devices. Patients undergoing Evolut R 34 mm implantation were excluded as no comparable prosthesis size for ACURATE neo is available. AA was evaluated with preprocedural computed tomography, and its impact on device success was evaluated. Results: In the overall population, AA did not have any impact upon device success, also when adjusting for in-study outcome predictors (odds ratio for 1° increment, 0.99 [95% CI, 0.98-1.01], P=0.306). However, increased AA was associated with lower device success with use of the Evolut R/PRO valves (odds ratio, 0.97 [95% CI, 0.95-0.99]; P=0.004), but not the ACURATE neo valves (odds ratio, 1.00 [95% CI, 0.98-1.03], P=0.304). The best AA cutoff value predicting device success was 49° (47% of the study cohort). Among patients with AA≥49°, Evolut R/PRO valves were associated with lower device success as compared to the ACURATE neo valve (inverse probability weighting odds ratio, 0.62 [95% CI, 0.46-0.83]; P=0.002). Conclusions: Horizontal aorta, as defined by an AA ≥49°, is a common feature among transcatheter aortic valve replacement candidates and predicts device failure of the Evolut R/PRO valves, but not of the ACURATE neo valve. AA may be an effect modifier of the association between self-expanding valve type and device success.