Abstract 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.