This study examined the impact of the Family Check-Up (FCU) and linked intervention services on reducing health-risk behaviors and promoting social adaptation among middle school youth. A total of 593 students and their families were randomly assigned to receive either the intervention or middle school services as usual. Forty-two percent of intervention families engaged in the service and received the FCU. Using complier average causal effect analyses, engagement in the intervention moderated intervention outcomes. Families who engaged in the intervention had youth who reported lower rates of antisocial behavior and substance use over time than did a matched control sample. Results extend previous research indicating that a family-centered approach to supporting youth in the public school setting reduced the growth of antisocial behavior, alcohol use, tobacco use, and marijuana use throughout the middle school years.