Nutrients included in commonly used dietary supplements, such as vitamins C and E, may affect cancer risk. To better understand how supplement use may affect the interpretation of cancer prevention trials, we examined dietary supplement use among participants in the Prostate Cancer Prevention Trial, a double-blind, placebo-controlled trial of the drug finasteride (Proscar) for the primary prevention of prostate cancer. Of 15,387 men who completed food frequency questionnaires and dietary supplement questionnaires, 44.3% used a multivitamin, 35% used single supplements of vitamin C or E, and 10-15% used antioxidant mixtures or single supplements of vitamins A and D, zinc, or beta-carotene at least three times per week. The strongest correlates of supplement use were higher education and lower body mass index (p < 0.001), and whites and Asians were more likely to use multivitamins and single supplements of vitamins C and E than were blacks and Hispanics. Supplement users obtained 87% of their total daily vitamin E intake, 61-64% of vitamins A, C, and D, and about half of beta-carotene, folate, and zinc from supplements. Because supplements, especially antioxidants, may confer independent cancer-preventive effects, analytic models of study findings should include exposure measurement of dietary supplements with appropriate tests for interaction. Our results can be generalized to similar chemoprevention trials.