Prevention of the early onset of disease is an important strategy for confronting America's co-occurring problems of increasing health care spending and increasing burden of disease as the population ages. Communities That Care is a prevention system created to provide training and materials that mobilize and empower coalitions of diverse community stakeholders to prevent adolescent drug use and delinquency. This report is the first randomized trial of Communities That Care, conducted in 24 communities in 7 states. Students in intervention communities were less likely to initiate use of alcohol, cigarettes, and smokeless tobacco than those in the control communities and were less likely to initiate delinquent behavior. This study indicates that public health can be promoted and risky behaviors in early adolescence can be prevented by coalitions of community stakeholders.