OBJECTIVES: The authors sought to evaluate the impact of transapical (TA) transcatheter aortic valve replacement (TAVR) on mortality, left ventricular (LV) ejection fraction (LVEF) improvement, and functional recovery in patients with LV dysfunction. BACKGROUND: LV injury inherent to TA access for structural heart disease interventions may be particularly detrimental to the LV, functional recovery, and survival in patients with LV dysfunction. METHODS: The study included patients enrolled within the PARTNER I (Placement of Aortic Transcatheter Valves) trial that underwent transfemoral (TF) or TA TAVR. Analyses of clinical outcomes were stratified by the presence of baseline LV dysfunction (LVEF<50%) and adjusted for the propensity of receiving TA TAVR. RESULTS: Of 2,084 subjects, 1,057 underwent TA TAVR. TA access was associated with increased 2-year all-cause mortality in those with (adjusted hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.12 to 2.07; p = 0.008) and without (HR: 1.38; 95% CI: 1.10 to 1.74; p = 0.006) LV dysfunction. TA TAVR portended increased 2-year cardiac mortality in subjects with LVEF<50% (HR: 1.92; 95% CI: 1.21 to 3.05; p = 0.006), but not with LVEF≥50% (HR: 1.29; 95% CI: 0.87 to 1.90; p = 0.21). In those with LVEF<50%, greater improvements in LVEF (TF-TA difference +4.04%, 95% CI: 2.39% to 5.69%; p < 0.0001) and 6-min walk distance (TF-TA difference +45.1 m, 95% CI: 18.4 to 71.9 m; p = 0.001) occurred within 30 days after TF versus TA TAVR. CONCLUSIONS: Compared with TF TAVR, TA TAVR is associated with a disproportionate risk of cardiac mortality in patients with LV dysfunction and with delayed and less robust improvement in LV function and overall functional status. Caution is warranted when considering TA access for structural heart disease interventions, particularly in patients with LV dysfunction. (Placement of Aortic Transcatheter Valves [PARTNER]; NCT00530894).