This article reports results of a meta-analysis of the effects of a set of community coalitions that implemented science-based substance use prevention interventions as part of a State Incentive Grant (SIG) in Kentucky. The analysis included assessment of direct effects on prevalence of substance use among adolescents as well as assessment of what "risk" and "protective" factors mediated the coalition effects. In addition, we tested whether multiple science-based prevention interventions enhanced the effects of coalitions on youth substance use. Short-term results (using 8th-grade data) showed no significant decreases in six prevalence of substance use outcomes -- and, in fact, a significant though small increase in prevalence of use of one substance (inhalants). Sustained results (using 10th-grade data), however, showed significant, though small decreases in three of six substance use outcomes -- past month prevalence of cigarette use, alcohol use, and binge drinking. We found evidence that the sustained effects on these three prevalence outcomes were mediated by two posited risk factors: friends' drug use and perceived availability of drugs. Finally, we found that the number of science-based prevention interventions implemented in schools within the coalitions did not moderate the effects of the coalitions on the prevalence of drug use. Study limitations are noted.