OBJECTIVE: To determine predictors and health-related motivation for supplement use. DESIGN: Population-based, cross-sectional survey. Food intake was determined by a validated food frequency questionnaire that included questions on dietary supplement consumption. Physical activity, smoking status, educational level, self-perceived mental and physical health, and medical information and drug treatment of diabetes, hypertension, and hypercholesterolemia were recorded. Weight and height were measured. SETTING: Girona, Spain. PARTICIPANTS: Six thousand three hundred fifty-two men and women aged 35-80 years. ANALYSIS: Multiple logistic regression analysis to evaluate the association between dietary supplement use and the other variables. RESULTS: Dietary supplements were consumed by 9.3% of the participants. Positive predictors of supplement use were female sex (odds ratio = 2.44, 95% confidence interval 1.96-3.04), higher educational level (P < .001), and a high adherence to the Mediterranean diet pattern (P < .001) and to the nutrient adequacy score (P = .004). A higher body mass index (P < .001) and the awareness of hypertension (odds ratio = 0.69, 95% confidence interval 0.56-0.87) were negatively associated with supplement use. CONCLUSIONS AND IMPLICATIONS: The relatively small number of dietary supplement users did not show a clustering of healthy lifestyle habits. Self-perception of mental and physical health and awareness of a cardiometabolic disorder were not motivators for supplement use.