The Monitored Atherosclerosis Regression Study (MARS) was a randomized, double-blind, placebo-controlled angiographic trial of lipid-lowering therapy in subjects with coronary artery disease. Subjects were counseled to follow a low-fat, low-cholesterol diet. At every clinic visit, data were obtained on body weight, dietary intake, alcohol consumption, and tobacco use. Semiannual determinations of early preintrusive atherosclerosis were made with high-resolution B-mode ultrasonography of the carotid artery intima-media thickness (IMT). We evaluated the effects of lifestyle modification (diet, alcohol, smoking, and weight loss) on the rate of carotid artery IMT progression on the 94 subjects randomly assigned to the placebo group. Dietary cholesterol, insoluble fiber, body mass index, and smoking were significant predictors of the annual rate of carotid artery IMT progression (P < 0.05). For subjects experiencing IMT progression, increased intakes of monounsaturated fat relative to saturated fat and stearic acid (18:0) consumption were significant predictors of a reduction in the annual rate of carotid artery IMT progression; for subjects experiencing IMT regression, male sex was a significant predictor of a reduction in the annual rate of carotid artery IMT regression. Modifications reducing body mass index by 5 kg/m2, quitting a 10 cigarette/d smoking habit, and reducing dietary cholesterol intake by 100 mg/d on average would reduce the annual rate of carotid wall IMT progression by 0.13 mm/y, which is equivalent to the maximum rate of IMT progression observed in the MARS placebo group. Progression of early preintrusive atherosclerosis can be reduced and overall regression can occur with dietary and lifestyle modification.