BACKGROUND: Mean transaortic pressure gradient (MTPG) has never been validated as a predictor of mortality in patients with severe aortic stenosis. We sought to determine the value of MTPG to predict mortality in a large prospective cohort of severe aortic stenosis patients with preserved left ventricular ejection fraction and to investigate the cutoff of 60 mm Hg, proposed in American guidelines. METHODS AND RESULTS: A total of 1143 patients with severe aortic stenosis defined by aortic valve area ≤1 cm2 and MTPG ≥40 mm Hg were included. The population was divided into 3 groups according to MTPG: between 40 and 49 mm Hg, between 50 and 59 mm Hg, and ≥60 mm Hg. The end point was all-cause mortality. MTPG was ≥60 mm Hg in 392 patients. Patients with MTPG ≥60 mm Hg had a significantly increase risk of mortality compared with patients with MTPG <60 mm Hg (hazard ratio [HR]=1.62 [1.27-2.05] P<0.001), even for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.56 [1.04-2.34] P=0.032). After adjustment for established outcome predictors, patients with MTPG ≥60 mm Hg had a significantly higher risk of mortality than patients with MTPG <60 mm Hg (HR=1.71 [1.33-2.20] P<0.001), even after adjusting for surgery as a time-dependent variable (HR=1.71 [1.43-2.11] P<0.001). Similar results were observed for the subgroup of asymptomatic or minimally symptomatic patients (HR=1.70 [1.10-2.32] P=0.018 and HR=1.68 [1.20-2.36] P=0.003, respectively). CONCLUSIONS: This study shows the negative prognostic impact of high MTPG (≥60 mm Hg), on long-term outcome of patients with severe aortic stenosis with preserved left ventricular ejection fraction, irrespective of symptoms.