The Drug Abuse Resistance Education (D.A.R.E.) program is a widespread but controversial school-based drug prevention program in the United States as well as in many other countries. The present multivariate meta-analysis reviewed 20 studies that assessed the effectiveness of the D.A.R.E. program in the United States. The results showed that the effects of the D.A.R.E. program on drug use did not vary across the studies with a less than small overall effect while the effects on psychosocial behavior varied with still a less than small overall effect. In addition, the characteristics of the studies significantly explained the variation of the heterogeneous effects on psychosocial behavior, which provides empirical evidence for improving the school-based drug prevention program.