The aim of this study was to investigate medicine use and associated factors among adolescents. This was a prospective cohort study including 4,452 adolescents born in Pelotas, Rio Grande do Sul State, Brazil, in 1993. Information on medicine use in the 15 days prior to the interviews was collected from the mothers. Overall prevalence of medicine use was 30.9%, and 64.7% of the medicines had been prescribed by a physician. The most frequently used pharmacological groups were medicines for the nervous (35.9%) and respiratory systems (25.7%). Medicine use was directly associated with socioeconomic status, maternal schooling, complications during pregnancy or delivery, and neonatal problems resulting in the need for intensive care. Underweight and obese adolescents were more likely to use medicines as compared to those with normal body mass index. A direct association was observed between maternal use of hypnotic drugs and sedatives and adolescent medicine use. It is essential to implement educational policies aimed at promoting rational use of medicines by adolescents.