Purpose: To examine the characteristics and effects of culturally adapted substance use interventions with Latino adolescents on substance use outcomes. Methods: Systematic review and meta-analytic methods were used to synthesize effects across studies on substance use outcomes at posttest and follow-up time points. Results: Ten studies comprising 12,546 Latino adolescents met eligibility criteria. Meta-analytic results suggest positive, yet small effects on substance use outcomes at posttest and slightly larger effects at follow-up. A moderate amount of heterogeneity was observed; however, no variables tested explained the variance. The risk of bias assessment revealed that most studies were at high risk for performance and selection bias. Conclusions: Culturally adapted substance use interventions with Latino adolescents may be slightly more effective than other active interventions. We also uncovered important gaps and deficiencies in this body of research, including the need to examine potential secondary benefits of culturally adapted interventions.