This 5-year follow-up of a randomized clinical trial evaluated the efficacy of a family-focused intervention delivered in middle school to increase school engagement following transition to high school (2 years post-test), and also evaluated mediated effects through school engagement on multiple problem outcomes in late adolescence (5 years post-test). The study sample included 516 Mexican American adolescents who participated in a randomized trial of the Bridges to High School Program (Bridges/Puentes). Path models representing the direct and indirect effects of the program on four outcome variables were evaluated using school engagement measured in the 9th grade as a mediator. The program significantly increased school engagement, with school engagement mediating intervention effects on internalizing symptoms, adolescent substance use, and school dropout in late adolescence when most adolescents were in the 12th grade. Effects on substance use were stronger for youth at higher risk based on pretest report of substance use initiation. There were no direct or indirect intervention effects on externalizing symptoms. Findings support that school engagement is an important prevention target for Mexican American adolescents.