Abstract Background The importance of transcatheter heart valve (THV) design on clinical outcome in patients with aortic stenosis (AS) and left ventricular (LV) systolic dysfunction remains unknown. Objectives We aimed to compare 5-year outcomes of patients with severe AS and reduced LV ejection fraction (LVEF), undergoing transcatheter aortic valve replacement (TAVR) with balloon-expandable vs. self-expanding THVs. Methods In an institutional TAVR registry, patients with LVEF <50% who underwent TAVR with either balloon-expandable or self-expanding THVs were included. A 1:1 propensity-score matching was performed to account for baseline differences between groups. Results A total of 759 patients were included between August 2007 and December 2022, and propensity-score matching resulted in 134 pairs. Technical success was achieved in over 85% of patients, and was similar in both groups. Self-expanding THVs were associated with a lower mean transvalvular gradient (7.1 ± 3.7 mmHg vs. 9.9 ± 4.3 mmHg; P <0.001) and a higher incidence of ³mild-to-moderate paravalvular regurgitation (36.3% vs. 11.3%; P <0.001) compared to balloon-expandable THVs. At 5 years, patients treated with a self-expanding THV had higher all-cause mortality than those with a balloon-expandable THV (67.8% vs. 55.8%, Adjusted Hazard Ratio: 1.44; 95% CI: 1.02-2.03; P = 0.037). There were no significant differences in other clinical outcomes up to 5 years between groups. Conclusions In the setting of LV systolic dysfunction, patients treated with a self-expanding THV had higher risk of 5-year mortality compared to patients treated with a balloon-expandable THV.