The use of dietary supplements has increased substantially in most industrialized countries. The aim of this study was to prospectively examine the association between use of dietary supplements and all-cause mortality, cancer mortality and CVD mortality in men. We used the population-based prospective cohort of 38 994 men from central Sweden, 45-79 years of age, with no cancer or CVD at baseline and who completed a self-administered FFQ including questions on dietary supplement use and life-style factors in 1997. During average 7.7 years of follow-up, 3403 deaths were ascertained; among them, 771 due to cancer and 930 due to CVD (during 5.9 years of follow-up). In multivariate adjusted models including all men there was no association observed between use of any dietary supplement or of multivitamins, vitamin C, vitamin E or fish oil specifically and all-cause mortality, cancer or CVD mortality. Among current smokers, regular use of any supplement was associated with statistically significant increased risk of cancer mortality: relative risk (RR) 1.46 (95 % CI 1.06, 1.99). Among men reporting an inadequate diet at baseline (assessed by Recommended Food Score), there was a statistically significant inverse association between use of any dietary supplement and CVD mortality (RR 0.72; 95 % CI 0.57, 0.91), no associations were observed among men with adequate diets. In conclusion, we cannot exclude that the use of dietary supplements is harmful for smokers. On the other hand, among men with an insufficient diet, the use of supplements might be beneficial in reducing CVD mortality.