Substance use outcomes were examined for 351 youth participating in a randomized controlled trial designed to assess the efficacy of a school-based multimodal universal preventive intervention, Linking the Interests of Families and Teachers (LIFT). Frequency of any use of tobacco, alcohol, and other drugs was assessed via self-report from grades 5 through 12. Latent variable growth models specified average level, linear growth and accelerated growth. The LIFT intervention had a significant effect on reducing the rate of growth in use of tobacco and illicit drugs, particularly for girls, and had an overall impact on average levels of use of tobacco, alcohol, and illicit drugs. Average tobacco use reductions were mediated by increases in family problem solving. The intervention had significant indirect effects on growth in substance use through intervention effects on reduced playground aggression and increased family problem solving. The intervention was also associated with roughly a 10 percent reduced risk in initiating tobacco and alcohol use. Implications for future studies of multimodal preventive interventions are discussed. (Published Abstract) 56 references