OBJECTIVE: To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants. DESIGN: Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort). SETTING: Western Washington State. PARTICIPANTS: A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. RESULTS: Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamin use and melanoma risk in women (RR, 1.14; 95% CI, 0.78-1.66) or in men (RR, 1.09; 95% CI, 0.83-1.43). Moreover, we did not observe increased melanoma risk with the use of supplemental beta carotene (RR, 0.87; 95% CI, 0.48-1.56) or selenium (RR, 0.98; 95% CI, 0.69-1.41) at doses comparable with those of the SUVIMAX study. Conclusion Antioxidants taken in nutritional doses do not seem to increase melanoma risk.