This study was designed to quantitatively evaluate the effectiveness of motivational interviewing (MI) interventions for adolescent substance use behavior change. Literature searches of electronic databases were undertaken in addition to manual reference searches of identified review articles. Databases searched include PsycINFO, PUBMED/MEDLINE, and Educational Resources Information Center. Twenty-one independent studies, representing 5,471 participants, were located and analyzed. An omnibus weighted mean effect size for all identified MI interventions revealed a small, but significant, posttreatment effect size (mean d = .173, 95% CI [.094, .252], n = 21). Small, but significant, effect sizes were observed at follow-up suggesting that MI interventions for adolescent substance use retain their effect over time. MI interventions were effective across a variety of substance use behaviors, varying session lengths, and different settings, and for interventions that used clinicians with different levels of education. The effectiveness of MI interventions for adolescent substance use behavior change is supported by this meta-analytic review. In consideration of these results, as well as the larger literature, MI should be considered as a treatment for adolescent substance use.