INTRODUCTION: Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease. The Homocysteine Lowering Trialists' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25%. Aim of this study was to investigate the effect of daily supplementation of folic acid (5 mg) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor.METHODS: We enrolled 103 patients with at least one cardiovascular risk factor who were randomized to receive either a daily dose of 5 mg folic acid (group I, n=53) or placebo (group II, n=50) for 18 months.RESULTS: After 18 months of folic acid supplementation, homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group. Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter. Significant regression of carotid IMT was observed (0.961+/-0.092 to 0.933+/-0.077 mm, p<0.001) compared to significant IMT progression in the placebo group (0.964+/-0.099 to 0.984+/-0.094 mm).CONCLUSION: Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk.