We examined the effects of folate (either alone or co-supplemented with Vitamin E) on endothelial function in hyperhomocysteinimic patients and correlated results with serum antioxidant capacity. A randomized trial was carried out in 30 young patients with recent acute myocardial infarction (AMI) and high plasma homocysteine concentrations. Intervention consisted of high doses of folate, either alone (group A) or in combination with Vitamin E (group B), for three months. Main outcome measures were endothelial function, serum antioxidant capacity, and homocysteinemia. Folic acid treatment reduced plasma homocysteine concentrations in both groups by 41% and, as compared with baseline values, was associated with a significant (P<0.001) improvement of endothelial function (from 0.322 (0.03) to 0.450 (0.02)mm in group A and from 0.338 (0.03) to 0.584 (0.04)mm in group B). However, there was no difference in endothelial function improvement between folic acid and folic acid plus Vitamin E group. Plasma antioxidant capacity significantly (P<0.001) increased in both groups. In conclusion, beneficial effects of folic acid on vasomotion appear to be independent of antioxidant action but, rather, seem to be strongly associated with reduction of homocysteinemia. Confirming previous reports, the effects of Vitamin E are still equivocal.