OBJECTIVES: Vitamin and mineral supplementation is a common practice in the United States, yet little is known about the long-term health effects of regular supplement use. METHODS: To examine the relationship between reported use of supplements and mortality, we analyzed data from US adults 25 to 74 years of age who were examined in the First National Health and Nutrition Examination Survey (1971 to 1975), with vital status determined through 1987. RESULTS: At baseline, 22.5% of the cohort reported using supplements regularly and 10.0% reported irregular use. The risk of mortality for regular supplement users was similar to that for nonusers. No consistent mortality benefits or risks of supplement use were found across a number of population subgroups. The risk for those who reported supplement use at both the baseline and a follow-up interview approximately 10 years later was similar to the risk for those who reported not using supplements at either interview. CONCLUSIONS: We found no evidence of increased longevity among vitamin and mineral supplement users in the United States. Considering the wide use of supplements in the general population, the cost-effectiveness and the safety of supplement use need to be better defined.