This study used Complier Average Causal Effect analysis (CACE; see G. Imbens & D. Rubin, 1997) to examine the impact of an adaptive approach to family intervention in the public schools on rates of substance use and antisocial behavior among students ages 11-17. Students were randomly assigned to a family-centered intervention (N = 998) in 6th grade and offered a multilevel intervention that included (a) a universal classroom-based intervention, (b) the Family Check-Up (selected; T. J. Dishion & K. Kavanagh, 2003), and (c) family management treatment (indicated). All services were voluntary, and approximately 25% of the families engaged in the selected and indicated levels. Participation in the Family Check-Up was predicted by 6th-grade teacher ratings of risk, youth reports of family conflict, and the absence of biological fathers from the youths' primary home. Relative to randomized matched controls, adolescents whose parents engaged in the Family Check-Up exhibited less growth in alcohol, tobacco, and marijuana use and problem behavior during ages 11 through 17, along with decreased risk for substance use diagnoses and police records of arrests by age 18.