Random assignment was made of 182 clinically referred marijuana- and alcohol-abusing adolescents to one of three treatments: multidimensional family therapy (MDFT), adolescent group therapy (AGT), and multifamily educational intervention (MEI). Each treatment represented a different theory base and treatment format. All treatments were based on a manual and were delivered on a once-a-week outpatient basis. The therapists were experienced community clinicians trained to model-specific competence prior to the study and then supervised throughout the clinical trial. A theory-based multimodal assessment strategy measured symptom changes and prosocial functioning at intake, termination, and 6 and 12 months following termination. Results indicate improvement among youths in all three treatments, with MDFT showing superior improvement overall. MDFT participants also demonstrated change at the 1-year follow-up period in the important prosocial factors of school/academic performance and family functioning as measured by behavioral ratings. Results support the efficacy of MDFT, a relatively short-term, multicomponent, multitarget, family-based intervention in significantly reducing adolescent drug abuse and facilitating adaptive and protective developmental processes.