BACKGROUND: Laboratory and observational studies suggest that antioxidant and B vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques. OBJECTIVE: The objective was to perform a meta-analysis of randomized controlled trials of the effect of vitamin-mineral supplementation on atherosclerosis progression. DESIGN: We searched the MEDLINE, EMBASE, and CENTRAL databases for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidants (vitamins E and C, beta-carotene, or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group. RESULTS: In trials not involving percutaneous transluminal coronary angioplasty, the pooled effect size was -0.06 (95% CI: -0.20, 0.09; 7 trials) for antioxidants and -0.93 (95% CI: -2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous transluminal coronary angioplasty, the pooled relative risk of restenosis was 0.82 (95% CI: 0.54, 1.26; 3 trials) for antioxidants and 0.84 (95% CI: 0.34, 2.07; 2 trials) for B vitamins. CONCLUSION: Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events.