The present study investigated whether a life skills program (LSP) for the prevention of adolescent substance misuse can have positive influences on a school context and on school bonding. The study also explored whether effects on alcohol use are mediated by positive effects on school bonding resulting from program participation. The LSP IPSY (Information + Psychosocial Competence = Protection) was implemented over a 3-year period via specially trained teachers. Analyses were based on a German evaluation study utilizing a quasi-experimental design (intervention/control) with school-wise assignment to the respective groups. Analyses were based on four measurement points (N = 952, 10 years at pre-test). Results indicated that IPSY was well implemented, highly accepted by teachers and students, and that teachers profited regarding their teaching methods. ANCOVAS revealed positive program effects on alcohol use and school bonding. Multiple regressions indicated that positive influences on school bonding following program participation partially mediated effects on alcohol use. (Contains 4 tables.)