Despite the popularity and perceived potential effectiveness of community-based coalitions in helping to prevent and reduce adolescent substance use, empirical evidence supporting this approach is sparse. Many reasons have been suggested for why coalition-based prevention initiatives, and community-level interventions in general, have not demonstrated stronger and more consistent results. Among these explanations are lack of uniformity and control over activities implemented by coalitions and inadequate numbers of communities used in evaluative studies. This article reports findings from the evaluation of a nonrandomized community trial in Vermont in which 23 community coalitions were funded for 3 years to select and implement a comprehensive mix of research-based prevention strategies designed to reduce substance use prevalence among adolescents. Data from three successive biennial administrations of the statewide Youth Risk Behavior Survey were used to assess this goal. Across the communities served by these coalitions, greater reductions in student substance use prevalence were achieved, relative to the remainder of the state, for all nine substance use measures examined. The greatest relative reductions were observed for past-30-day use of marijuana and cigarettes (both p less than 0.05). These findings suggest that collaborative community-based efforts implemented within a supportive framework such as Vermont's New Directions project can have a meaningful impact on the prevalence of substance use behaviors among youth. (Contains 5 tables and 1 figure.)