The Kuopio Atherosclerosis Prevention Study is the first population-based, double-blind trial in the primary prevention of carotid and femoral atherosclerosis. A total of 447 subjects with serum low density lipoprotein (LDL) cholesterol levels ≥155 mg/dl (≥4.0 mmol/liter) and total cholesterol levels <290 mg/dl (<7.5 mmol/liter) were randomly assigned to receive either pravastatin 40 mg/day or placebo for 3 years. Atherosclerotic progression in 424 men was assessed with B-mode ultrasonography. Pravastatin reduced the rate of progression by 45% (95% confidence interval [CI]: 16–69%, p = 0.005) in carotid arteries and by 66% (95% CI: 30–90%, p = 0.002) in the common carotid arteries. The treatment effect in the carotid arteries was greater in subjects with thick arterial walls at baseline, in smokers, and in subjects with low plasma α-tocopherol. Subjects who received pravastatin had a higher antioxidative capacity of LDL, a longer oxidation lag of very low density lipoprotein (VLDL) plus LDL, and a reduced oxidation rate of VLDL plus LDL in vitro. These data establish the antiatherogenic effect of lowering LDL cholesterol levels by pravastatin therapy in hypercholesterolemic men in a primary prevention setting and suggest that part of the antiatherogenic effect of pravastatin may be due to an improvement in the resistance of atherogenic lipoproteins to oxidation.