Lifestyle modifications are the crux of atherosclerotic disease management. The goal of this study was to determine the effectiveness of diet and exercise in decreasing coronary and carotid atherosclerotic burden. Randomized controlled trials examining the effects of intensive lifestyle measures on atherosclerotic progression in coronary and carotid arteries as measured by baseline and follow-up quantitative coronary angiogram and ultrasonographic carotid intimal-medial thickness (CIMT), respectively, were included. Studies were excluded if the intervention additionally included a medication. MEDLINE, EMBASE, CINAHL, Cochrane Controlled Trials Registers, reports, and abstracts from major cardiology meetings were searched by 2 researchers independently and verified by the primary investigator. Standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated using random-effects model. Publication bias and heterogeneity were assessed. Fourteen trials were included. Seven used quantitative coronary angiogram, and 7 used CIMT; 1,343 lesions in 340 patients in the coronary group and 919 patients in the carotid group were analyzed. Overall, lifestyle modifications were associated with a decrease in coronary atherosclerotic burden in percent stenosis by −0.34 (95% CI −0.48 to −0.21) SMD, with no significant publication bias and heterogeneity (p = 0.21, I² = 28.25). Similarly, in the carotids, there was a decrease in the CIMT, in millimeter, by −0.21 (95% CI −0.36 to −0.05) SMD and by −0.13 (95% CI −0.25 to −0.02) SMD, before and after accounting for publication bias and heterogeneity (p = 0.13, I² = 39.91; p = 0.54, I² = 0), respectively. In conclusion, these results suggest that intensive lifestyle modifications are associated with a decrease in coronary and carotid atherosclerotic burden.