OBJECTIVE Two-year longitudinal follow-up data evaluated the behavioral impact of Resilient Families, a universal intervention that aimed to prevent early initiation and frequent and heavy adolescent alcohol use in secondary schools in Melbourne, Australia. METHODS Of 24 secondary schools (62% of those approached), 12 were randomly assigned to intervention and 12 as controls. Intervention students received a social relationship curriculum; their parents received parent education handbooks and invitations to parent education events outlining strategies to encourage healthy adolescent development and reduce adolescent alcohol misuse. At Wave 1 (2004), students were in Year 7 secondary school (mean age, 12.3 years). Data were imputed for students completing at least two of three annual surveys (N = 2,354). Wave 3 (2006; mean, 14.5 years) main outcome measures for alcohol use were "any," "frequent" (at least monthly), and "heavy" (five or more drinks in a session at least once in the prior fortnight). Multivariate logistic regression assessed intervention exposure effects, adjusting for school classroom clustering and baseline measures. RESULTS Relative to controls, intervention students showed significant reductions in any lifetime use (adjusted odds ratio [AOR], .78; 95% confidence interval [CI], .62-.97), and reduced progression to frequent (AOR, .69; CI, .56-.86) and heavy use (AOR, .75; CI, .60-.94). CONCLUSIONS Randomized assignment to Resilient Families was associated with a significant reduction in adolescent alcohol use among families volunteering for the evaluation. Family-school-based interventions appear promising as a strategy to contribute to population reductions in currently high rates of adolescent alcohol misuse.