BACKGROUND: Although regular physical activity is recommended for prevention of cardiovascular diseases, no data are available on its antiatherosclerotic effects in the general population. OBJECTIVE: To determine whether progressive aerobic exercise compared with usual activity slows progression of atherosclerosis in men. DESIGN: A 6-year randomized, controlled trial. SETTING: Eastern Finland. PARTICIPANTS: 140 middle-aged men randomly selected from the population registry. INTERVENTION: Low- to moderate-intensity aerobic exercise. MEASUREMENTS: Atherosclerosis was quantitated ultrasonographically as the mean intima-media thickness in the carotid artery at baseline and at years 2 through 6. RESULTS: On the basis of intention-to-treat analyses, a 19.5% net increase (P < 0.001) in ventilatory aerobic threshold was evident in the exercise group after 6 years. High-sensitivity C-reactive protein levels were statistically nonsignificantly lower in the exercise group than in the control group (P > 0.2). The progression of intima-media thickness in the carotid artery did not differ between the study groups (P > 0.2). A subgroup analysis that excluded men taking statins showed that the 6-year progression of intima-media thickness, adjusted for smoking and annual measures of low-density lipoprotein cholesterol level, systolic blood pressure, and waist circumference, was 40% less in the exercise group (0.12 mm [95% CI, -0.010 to 0.26 mm]) than in the control group (0.20 mm [CI, 0.05 to 0.35 mm]). LIMITATIONS: Only middle-aged white men were included. The intervention included mainly aerobic exercises. CONCLUSIONS: Aerobic physical exercise did not attenuate progression of atherosclerosis, except in a subgroup of men not taking statins.