Vitamin E, a naturally occurring antioxidant, has been found to reduce atherosclerotic lesion formation in animal models as well as cardiovascular morbidity in several observational studies. However, a number of case-control and prospective cohort studies failed to confirm its value in the primary and secondary prevention of morbidity and mortality from coronary artery disease. Several small or larger randomized interventional trials completed to date failed to resolve the conflict. Notably, even in large, well-conducted prospective epidemiologic studies, the potential effects of residual confounding may be on the same order of magnitude as the reported benefit. The response to vitamin E supplementation in specific patient subpopulations with chronic inflammation and/or higher degrees of oxidative stress has not been studied as yet. Therefore, further large randomized interventional trials are warranted to clarify accurately the role of vitamin E in the primary and secondary prevention of atherosclerotic coronary disease in these patient groups.