It has been suggested that statins could slow the progression of aortic stenosis (AS), but this hypothesis is still debated and has not been validated in large series of patients by long-term follow-up studies. Moreover, information about the role of statins in patients with different degrees of severity of AS is scarce. From our 1988 to 2007 echocardiographic database, we retrospectively identified all asymptomatic patients with aortic valve sclerosis (abnormal irregular thickening of the aortic valve with a peak aortic velocity [Vmax] > or =1.5 and <2 m/s), mild AS (Vmax > or =2 and <3 m/s), and moderate AS (Vmax > or =3 and <4 m/s), age > or =50 years, and with > or =2 echocardiographic studies > or =2 years apart. Exclusion criteria were moderate/severe aortic regurgitation, bicuspid aortic valve, rheumatic valve disease, and ejection fraction <40%. The final study population consisted of 1,046 patients (mean age 70 +/- 8 years, 587 men); 309 were treated with statins. Mean follow-up duration was 5.6 +/- 3.2 years (range 2 to 19). Progression of AS was slower in patients receiving statins compared with untreated patients in aortic sclerosis (0.04 +/- 0.09 vs 0.07 +/- 0.10 m/s/year, p = 0.01) and mild AS (0.09 +/- 0.15 vs 0.15 +/- 0.15 m/s/year, p = 0.001), but not in moderate AS (0.21 +/- 0.18 vs 0.22 +/- 0.15 m/s/year, p = 0.70). In multivariate analysis only statin therapy, initial Vmax, and dialysis were independently related to progression of aortic valve disease. In conclusion, in a large series of patients with long-term follow-up, statins were effective in slowing the progression of aortic valve disease in aortic sclerosis and mild AS, but not in moderate AS. These results suggest that statin therapy should be taken into consideration in the early stages of this common disease.