OBJECTIVE: To assess the association between the use of multivitamins and prostate cancer mortality. METHODS: A total of 5585 deaths from prostate cancer were identified during 18 years of follow-up of 475,726 men who were cancer-free and provided complete information on multivitamin use at enrollment in the Cancer Prevention Study II (CPS-II) cohort in 1982. Cox proportional hazards modeling was used to measure the association between multivitamin use at baseline and death from prostate cancer and to adjust for potential confounders. RESULTS: The death rate from prostate cancer was marginally higher among men who took multivitamins regularly (> or =15 times/month) compared to non-users (multivariate rate ratio=1.07, 95% CI: 0.99-1.15); this risk was statistically significant only for those multivitamin users who used no additional (vitamin A, C, or E) supplements (multivariate rate ratio=1.15, 95% CI: 1.05-1.26). In addition, risk was greatest during the initial four years of follow-up (1982-1986, multivariate rate ratio=1.12, 95 CI: 0.87-1.46). CONCLUSIONS: Regular multivitamin use was associated with a small increase in prostate cancer death rates in our study, and this association was limited to a subgroup of users.