The present study assessed the effect of age and co-morbidity on the outcomes of mild, moderate, and severe aortic stenosis (AS) in patients aged >60 years during 18 years of follow-up. The outcomes evaluated were hemodynamic progression, a composite cardiac mortality or aortic valve replacement (AVR) end point, and all-cause mortality. Consecutive Department of Veterans Affairs patients (aged >60 years) with AS were prospectively enrolled from 1988 to 1994 and followed until 2008 (n = 239). The baseline demographic, co-morbidity, and echocardiographic parameters were recorded. At enrollment, the mean age was 74 +/- 6 years, and 78% were men. The annualized mean aortic valve gradient progression was 4 +/- 4, 6 +/- 5, and 10 +/- 8 mm Hg for mild, moderate, and severe AS, respectively (p <0.001). During a mean follow-up of 8 +/- 5 years, 206 deaths (52% cardiac) and 91 AVRs were recorded. The AVR/cardiac mortality event rate at 1, 5, and 10 years was 2%, 26%, and 50% for mild AS, 13%, 63%, and 69% for moderate AS, and 66%, 95%, and 95% for severe AS (p <0.001). During the study period, 132 patients developed severe AS. The survival rate at 1, 5, and 10 years was 60 +/- 7%, 14 +/- 5%, and 5 +/- 3% with conservative management and 98 +/- 2%, 82 +/- 4%, and 50 +/- 5% after AVR, respectively (p <0.001). The independent predictors of all-cause mortality were the age-adjusted Charlson co-morbidity index (hazard ratio 1.24, p <0.001), AVR (hazard ratio 0.40, p <0.001), and grade of left ventricular dysfunction (hazard ratio 1.36, p = 0.01). In conclusion, the prognostic significance of AS is determined by the hemodynamic severity, left ventricular function, and the presence of symptoms, in the context of age and co-morbidities. The age-adjusted Charlson co-morbidity index provides crucial prognostic information to guide the surgical risk/benefit discussions for patients with severe AS. Crown Copyright (c) 2012 Published by Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:695-701)