Objective To assess the effect of B vitamins supplementation on cardiovascular and cerebrovascular diseases, and also to evaluate the relationship between homocysteine and risk of cardiovascular and cerebrovascular diseases. Methods Using the words ‘homocysteine’, ‘cardiovascular disease’, ‘cerebrovascular disease’, ‘B vitamins’, and ‘randomized controlled trial’, we searched PubMed, Ovid, and Springer. We also hand searched relevant journals and conference proceedings. Randomized controlled trials published between 1998 and July 2008 which evaluated the effect of B vitamins supplementation on vascular diseases were collected. Two reviewers independently screened trials, extracted data, and evaluated the quality of included trials. The Cochrane Collaboration’s RevMan 4.2 software was used for statistical analysis. Results Sixteen trials involving 27,043 patients with vascular disease were included. Results of meta-analyses showed that no significant differences were identified between the B vitamins group and the control group for each of the four endpoints, including the risk of cardiovascular events (RR 0.98, 95%CI 0.94 to 1.03), the risk of coronary heart disease (RR 0.99, 95%CI 0.92 to 1.07), the risk of stroke (RR 0.90, 95%CI 0.80 to 1.02), and the total mortality (RR 0.98, 95%CI 0.92 to 1.05). Sensitivity analyses conducted by a random effect model or with the exclusion of low-quality trials did not change the overall results. Conclusion The trials currently available cannot confirm the causal relationship between homocysteine and risk of cardiovascular and cerebrovascular diseases. More evidence from large-scale randomized controlled trials is needed to confirm this. There is not sufficient evidence to show that B vitamins supplementation can lower the risk of cardiovascular and cerebrovascular diseases. B vitamins supplementation should not be recommended for the secondary prevention of such diseases.