The prevalence of dietary supplement use varies largely among populations, and previous studies have indicated that it is high in the Danish population compared with other European countries. The diversity in supplement use across countries indicates that cultural and environmental factors could influence the use of dietary supplements. Only few studies investigating the use of dietary supplements have been conducted in the Danish population. The present cross-sectional study is based on 54 948 Danes, aged 50–64 years, who completed self-administrated questionnaires on diet, dietary supplements and lifestyle between 1993 and 1997. A health index including smoking, physical activity, alcohol and diet, and a metabolic risk index including waist circumference, urinary glucose and measured hypertension were constructed. Logistic regression was used to investigate these determinants in relation to the intake of dietary supplements. We found that 71 % of the participants were dietary supplement users; female sex, older age groups and higher educated participants were more likely to be users of any dietary supplements. One additional point in the health index was associated with 19, 16 and 9 % higher likelihood of being user of any, more common and less common supplements, respectively. In the metabolic risk index, one additional point was associated with 17 and 16 % lower likelihood of being user of any supplement and more common supplements, respectively. No significant association was found for less common supplement use. In conclusion, those with the healthiest lifestyle were more likely to use dietary supplements. Thus, lifestyle and dietary composition should be considered as confounders on supplement use and health outcomes.