OBJECTIVES: This study sought to examine whether the prognosis of patients with severe aortic stenosis (AS) having high versus low transvalvular mean pressure gradients (MPGs) is intrinsically different after transcatheter aortic valve replacement (TAVR), even after strict matching of baseline parameters. BACKGROUND: Patients with low MPG are characterized by higher cardiovascular risk and more comorbidities than other AS patients are. METHODS: In this retrospective, single-center study involving 2,282 patients, 3 groups were derived according to the following criteria: 1) high-gradient AS (HG-AS) (MPG ≥40 mm Hg); 2) low-flow, low-gradient AS (LFLG-AS) (MPG <40 mm Hg, ejection fraction [EF] ≤40%, stroke volume index ≤35 ml/m); 3) paradoxical LFLG-AS (pLFLG-AS) (similar to LFLG-AS but with EF ≥50%). Propensity score matching that included EF was used to compare 1-year survival. RESULTS: A total of 136 patients with HG-AS or LFLG-AS were identified. Kaplan-Meier survival curves were significantly different (p = 0.039), with death occurring in 11 versus 21 patients (hazard ratio: 2.12; 95% confidence interval: 1.02 to 4.39; p = 0.044), respectively. A total of 226 patients with HG-AS or pLFLG-AS were identified and here the curves were identical (p = 0.468), with death occurring in 18 versus 21 patients (hazard ratio: 1.26; 95% confidence interval: 0.67 to 2.38; p = 0.469). CONCLUSIONS: This is the first study comparing survival after TAVR of patients with high versus low MPG in matched study populations. Mortality in patients with LFLG-AS was twice that of HG-AS patients. However, it appears that patients with pLFLG-AS might benefit from TAVR to the same extent as patients with HG-AS. There must be still unmasked factors that influence mortality of patients with LFLG-AS.