Abstract Background: Reducing serum total cholesterol (TC) levels using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in hypercholesterolemic patients has been shown to reduce the incidence of complications of coronary heart disease (CHD). However, few data are available on the potential benefit of reductions in serum cholesterol levels in normocholesterolemic patients with coronary atherosclerosis. Objective: The Prevention of Coronary Sclerosis Study is a single-center study designed to assess the effect of treatment with the HMG-CoA reductase inhibitor pravastatin on progression and regression of angiographically documented coronary atherosclerosis in normocholesterolemic patients with CHD. Methods: A total of 329 patients aged <70 years with CHD were enrolled and classified into 1 of 3 groups based on serum TC level: group 1, TC ≥220 mg/dL; group 2, TC 180–219 mg/dL; and group 3, TC <180 mg/dL. Patients in group 2 were randomized to 1 of 2 subgroups, 2a or 2b. Patients in groups 1 and 2a were given pravastatin 10 mg/d; patients in groups 2b and 3 did not receive cholesterol-lowering drugs. The subsequent coronary events of patients were followed for 2 years and reexamined by coronary angiography (CAG). Both baseline and follow-up CAGs were analyzed by quantitative coronary arteriography at a central laboratory. Results: Decreases in both mean segment diameter (MSD) and minimum obstruction diameter (MOD) in group 2a were significantly less than those in the control group 2b ( P = 0.015 and P = 0.023, respectively). The effects on MSD and MOD in group 2a and the low-cholesterol reference group 3 were similar. The incidence of clinical events was 8.9%, 3.7%, 12.1%, and 10.0% in groups 1, 2a, 2b, and 3, respectively, with no significant differences in rates between groups 2a and 2b. Conclusion: The results of this study suggest that cholesterol-lowering therapy with pravastatin may prevent progression of coronary atherosclerosis in normocholesterolemic patients with CHD.