Epidemiological and experimental studies have indicated that dietary factors such as vitamin C, vitamin E, and beta-carotene are associated with the risk of colorectal cancer. This study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study), whose participants were randomly assigned to four supplementation groups: (a) alpha-tocopherol (AT), 50 mg/day; (b) beta-carotene (BC), 20 mg/day; (c) both AT and BC; and (d) placebo. We included the 15,538 ATBC Study participants who had been randomized within the areas of three major cities in southern Finland. Cases of colorectal adenoma (n = 146) were identified by the pathology laboratories in the study areas, and these participants' medical records were collected and reviewed. Alpha-tocopherol supplementation increased the risk for adenomas (relative risk, 1.66; 95% confidence interval, 1.19-2.32), whereas beta-carotene supplementation had no effect on the risk (relative risk, 0.98; 95% confidence interval, 0.71-1.35). Slightly more prediagnosis rectal bleeding and intestinal pain occurred in those adenoma cases who received alpha-tocopherol supplements than in those who did not. Thus, some bias may have resulted, with alpha-tocopherol supplementation leading to more colonoscopies and, thus, to an increased detection of incident polyps in this group. This is further supported by the trial finding that alpha-tocopherol supplementation did not increase the risk of colorectal cancer.