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Interventional trials with vitamin E have been planned on the assumption that it could reduce atherosclerotic progression via inhibition of oxidative stress. These trials have been conducted in patients at risk for or with cardiovascular disease, but the results have been divergent. The reason for the equivocal results is still unclear. We have recently demonstrated that in patients with hypercholesterolemia, the administration of a statin is associated with reduced urinary isoprostanes, a marker of oxidative stress, and normalization of circulating levels of vitamin E, indicating that statins enhance the antioxidant status. Based on these arguments, we reanalyzed the interventional trials with vitamin E to see if concomitant use of statins could have created a potential bias. We reviewed 9 interventional trials, each including >1000 patients. In 5 of the 9 trials, the concomitant use of statins was reported. In the arm randomized to vitamin E, a concomitant use of statins was reported in at least one-third of the population. In some trials, the percentage of patients given statins was >50%, suggesting that a large part of the follow-up population was likely useless treated with vitamin E in view of the concomitant antioxidant effect of statins. Also, the antiatherosclerotic effect of statins could have reduced the possibility that a prespecified sample size had an adequate power to observe a difference between vitamin E and placebo-treated groups. We therefore suggest that a meta-analysis of trials with vitamin E should be redone by excluding patients who concomitantly used statins.