Aims The aim of the present study was to determine the mediating role of affiliation with cannabis-using peers in the pathways from various dimensions of temperament to lifetime cannabis use, and to determine if these associations also contributed to the development of regular cannabis use. Methods Objectives were studied using data from 1300 participants of the Tracking Adolescents’ Individual Lives Survey (TRAILS), a large, general population study of Dutch adolescents. We used parentreports on the Early Adolescent Temperament Questionnaire to assess the dimensions high-intensity pleasure, shyness, fearfulness, frustration, and effortful control at age 10-12. By means of self-reports, lifetime and regular cannabis use were determined at age 15-18, and proportion of substance-using peers was determined at ages 12-15 and 15-18. Models were adjusted for age, sex, intelligence, and parental cannabis use. Results High-intensity pleasure (OR=1.09, 95%CI=1.05-1.13) and effortful control (OR=0.92, 95%CI=0.89-0.96) affected the risk for lifetime cannabis use through their influence on affiliation with cannabis-using peers. Shyness affected this risk independent from peer cannabis use. Only the pathway from effortful control was additionally associated with the development of regular cannabis use (OR=0.93, 95%CI=0.89-0.98). Conclusions Peer cannabis use and, to a lesser extent, certain temperamental characteristics affect an adolescents risk of cannabis use, and should be considered in prevention programs. We recommend future research to focus on factors that potentially modify the association between temperament, affiliation with cannabis-using peers and cannabis use.