Aim: Despite the substantial proportion of adolescents use medicine for common health problems, prevalence of medicine use among adolescents with migrant background have rarely been documented, and the causal pathway continue to be poorly understood. The aim was to examine whether there are migrant differences in adolescents’ medicine use for common health problems, and if feeling safe at school, as a non-exposure to discrimination, explained these differences. Methods: Data derived from the 2006 Danish contribution to the World Health Organization collaborative study Health Behaviour in School-aged Children (HBSC). Medicine use for headache, stomach-ache, difficulties getting to sleep and nervousness and feeling safe at school were self-reported. The population included boys and girls from ages 11 to 15 who were enrolled in the cross-sectional study. Included were 8480 ethnic Danes, 508 descendants and 456 migrants. Logistic regression was applied to assess associations. Multi-level logistic regression was used to assess the independent effect of school cluster. Results: Immigrant girls reported the highest past-month prevalence of medicine use for the four ailments included in the analysis. The highest prevalence of medicine use was found for alleviating headache (54.7%), followed by stomach-ache (30.4%). Among the boys who took medicine for stomach-ache, the odds were 2.11 (1.46-3.05) for descendants and 1.55 (1.00-2.39) for immigrants. Feeling safe at school modifies the effect by reducing the odds to 1.93 (1.32-2.81) for descendants and to 1.30 (0.81-2.07) for immigrants. When simultaneously controlling for the clustering effect of school, feeling safe at school and specific symptoms, the risk of using medicine for stomach-ache was still higher for descendant boys 1.90 (1.26-2.85). Conclusions: Self-reported medicine use for common health problems is high among adolescents with migrant background, particularly among first generations immigrant girls. Feeling safe at school partially mediated the association between migrant background and adolescent’s medicine use. As the process of migration is becoming more and more frequent, our findings suggest that more adolescents may be using medicines for reasons that cannot only be explained by frequency of symptoms alone.