The purpose of this study was to explore the effect of lifestyle modification, mainly daily aerobic exercise, on coronary atherosclerosis in patients with coronary artery disease (CAD). A 6-month prospective observational study was conducted with 84 CAD patients receiving pravastatin treatment in order to evaluate the relationship between lifestyle modification, in particular aerobic exercise, and plaque volume as assessed by intravascular ultrasound (IVUS). Lifestyle during the study period was assessed by the-lifestyle modification score. A significant decrease in plaque volume by 12.9% was observed after 6 months of pravastatin therapy (P<0.0001 vs baseline). The change in plaque volume correlated with the change in the serum level of high-density lipoprotein cholesterol (HDL-C) (r=-0.549, P<0.0001), non-HDL-C (r=0.248, P=0.03), low-density lipoprotein cholesterol/HDL-C (r=0.505, P<0.0001), apolipoprotein (apo) A-1 (r=-0.335, P=0.007) and apoB/apoA-1 (r=0.335, P=0.007), and lifestyle modification score (r=-0.616, P<0.0001). There was a clear positive correlation between a change in the serum HDL-C level and lifestyle modification score. Multivariate regression analysis revealed that the increase in serum HDL-C level and lifestyle modification score were independent predictors of coronary plaque regression. An appropriate combination of statin therapy and lifestyle modification, in particular, physical activity, may result in coronary plaque regression. This combined treatment strategy, inducing an increase of the serum HDL-C, may contribute to coronary plaque regression.