Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. ClinicalTrials.gov identifier: NCT00092677.