Objective: To examine whether students' school engagement, relationships with teachers, educational aspirations and involvement in fights at school are associated with various measures of subsequent substance use. Methods: Data were drawn from the Belfast Youth Development Study (n = 2968). Multivariate logistic models examined associations between school-related factors (age 13/14) and substance use (age 15/16). Results: The two factors which were consistently and independently associated with regular substance use among both males and females were student-teacher relationships and fighting at school: positive teacher-relationships reduced the risk of daily smoking by 48%, weekly drunkenness by 25%, and weekly cannabis use by 52%; being in a fight increased the risk of daily smoking by 54%, weekly drunkenness by 31%, and weekly cannabis use by 43%. School disengagement increased the likelihood of smoking and cannabis use among females only. Conclusion: Further research should focus on public health interventions promoting positive relationships and safety at school. (Contains 4 tables.)