Abstract: Objective To test whether the Communities That Care (CTC) prevention system reduces adolescent alcohol, tobacco, and other drug use and delinquent behavior communitywide. Design The Community Youth Development Study is the first randomized trial of CTC. Setting In 2003, 24 small towns in 7 states, matched within state, were randomly assigned to control or CTC conditions. Participants A panel of 4407 fifth-grade students was surveyed annually through eighth grade. Intervention A coalition of community stakeholders received training and technical assistance to install the CTC prevention system. They used epidemiological data to identify elevated risk factors and depressed protective factors in the community, and chose and implemented tested programs to address their community’s specific profile from a menu of effective programs for families, schools, and youths aged 10 to 14 years. Main Outcome Measures Incidence and prevalence of alcohol, tobacco, and other drug use and delinquent behavior by spring of grade 8. Results The incidences of alcohol, cigarette and smokeless tobacco initiation, and delinquent behavior were significantly lower in CTC than in control communities for students in grades 5 through 8. In grade 8, the prevalences of alcohol and smokeless tobacco use in the last 30 days, binge drinking in the last 2 weeks, and the number of different delinquent behaviors committed in the last year were significantly lower for students in CTC communities. Conclusion Using the CTC system to reduce health-risking behaviors in adolescents can significantly reduce these behaviors communitywide.