We conducted a prospective study on the association between supplemental vitamin E and colon cancer in 87,998 females from the Nurses' Health Study and 47, 344 males from the Health Professionals Follow-up Study. There was some suggestion that men with supplemental vitamin E intake of 300 IU/day or more may be at lower risk for colon cancer when compared with never users [multivariate relative risk (RR), 300-500 IU/day versus never users, 0.73 (95% confidence interval (CI), 0.52-1.03); >or=600 IU/day versus never users = 0.70 (95% CI = 0.38-1.29)], but CIs included 1. In women, there was no evidence for an inverse association between vitamin E supplementation and risk of colon cancer. Our findings do not provide consistent support for an inverse association between supplemental vitamin E and colon cancer risk. Considering the paucity of epidemiological data on this association, further studies of vitamin E and colon cancer are warranted.