Cross-sectional studies suggest that dietary supplement use is associated with favourable demographic and lifestyle factors and certain health conditions. However, factors that affect the consistency of supplement use have not been investigated in prospective cohort studies. The aim of the present study was to seek baseline demographic, lifestyle and health-status predictors of subsequent consistent vitamin and/or mineral supplement use. A total of 8968 men and 10,672 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort, who answered the supplement-use questions in the baseline survey and two follow-up surveys, were categorised into three groups: consistent, inconsistent and never users. At baseline, 28.5 % of men and 38.6 % of women reported vitamin and/or mineral supplement use. After a median follow-up of 8.5 years, 14.6 % of men and 22.9 % of women were consistent users. During follow-up, 36.0 % of male and 26.6 % of female initial users stopped supplement use, whereas 27.8 % of male and 39.4 % of female initial non-users started supplement use. Women were more likely to be consistent users than men. Older age (≥ 50 years), lower BMI (< 25 kg/m2) and self-reported hyperlipidaemia were common predictors of consistent use for both sexes. Additional predictors included higher educational level for men, and being more physically active and higher lifetime alcohol consumption for women. Consistent users had the highest intake of dairy products, fish, fruits and vegetables, and wine but the lowest intake of total meat. We concluded that supplement use is a fairly unstable behaviour in free-living individuals. Individuals with a favourable lifestyle and healthier diet are more likely to show consistent supplementation.