Objectives. To evaluate whether the effects of the Communities That Care (CTC) prevention system, implemented in early adolescence to promote positive youth development and reduce health-risking behavior, endured through age 21 years. Methods. We analyzed 9 waves of prospective data collected between 2004 and 2014 from a panel of 4407 participants (grade 5 through age 21 years) in the community-randomized trial of the CTC system in Colorado, Illinois, Kansas, Maine, Oregon, Utah, and Washington State. We used multilevel models to evaluate intervention effects on sustained abstinence, lifetime incidence, and prevalence of past-year substance use, antisocial behavior, and violence. Results. The CTC system increased the likelihood of sustained abstinence from gateway drug use by 49% and antisocial behavior by 18%, and reduced lifetime incidence of violence by 11% through age 21 years. In male participants, the CTC system also increased the likelihood of sustained abstinence from tobacco use by 30% and marijuana use by 24%, and reduced lifetime incidence of inhalant use by 18%. No intervention effects were found on past-year prevalence of these behaviors. Conclusions. Implementation of the CTC prevention system in adolescence reduced lifetime incidence of health-risking behaviors into young adulthood. Clinicaltrials.gov identifier: NCT01088542.