Observational studies have found that persons who consume large amounts of fruit and vegetables have lower rates of coronary heart disease. The strength of epidemiologic evidence, however, differs for each of the antioxidant vitamins. High intake of vitamin E from food or supplements has generally been associated with a lower incidence of coronary heart disease. The evidence for beta-carotene intake is inconsistent, with several studies finding a modest reduction in risk among persons with high intake, and others failing to find an association. Although many studies have examined the relationship between vitamin C intake and cardiovascular disease, no significant benefit was seen in any of the large studies that were able to control for other antioxidant intake or multivitamin use. Observational studies cannot discern whether the decreased risk observed is caused by the antioxidants themselves or other characteristics of the individuals who consume them. The epidemiologic associations may be due to other nutrients in antioxidant-rich foods, or other dietary or lifestyle factors. Randomized controlled trials are necessary to confirm or refute the observational data. On the basis of available evidence, we should recommend a healthy diet, rich in fruit and vegetables, but should not endorse vitamin supplementation unless conclusive evidence of benefit is demonstrated in clinical trials.