This study evaluated the efficacy of Integrated Family and Cognitive-Behavioral Therapy (IFCBT), a multisystems treatment for adolescent drug abuse, versus a Drugs Harm Psychoeducation curriculum (DHPE). A randomized controlled trial assessed youth and parents at baseline and at 1, 3 and 6-month posttreatment points. Youth participants (N=43) met diagnostic criteria for one or more psychoactive substance use disorders with most youth meeting criteria for alcohol and marijuana use disorders. IFCBT produced significant reductions in posttreatment substance use when compared against DHPE. Throughout the 6-month posttreatment period, youth receiving IFCBT used alcohol an average of 2.03 days each month, which was significantly lower than the average number of 6.06 days that DHPE youth used alcohol during the same period. Similarly, youth receiving IFCBT used marijuana an average of 5.67 days each month during the initial 6 posttreatment months which was also significantly lower than the average number of 13.83 days that DHPE youth used marijuana each month during the same period. IFCBT also reduced rates of any marijuana use and produced significant changes in targeted psychosocial risk and protective factors. IFCBT youth exhibited significantly higher levels of rational problem solving and learning strategy skills, and significantly lower levels of problem avoidance when compared with DHPE youths. IFCBT parents exhibited significantly more adaptive scores on communication, involvement, control, and values/norms indices when compared with DHPE parents. No iatrogenic effects were exhibited among youth in either IFCBT or DHPE conditions on the outcome measures examined. The present study findings suggest that IFCBT is a promising approach for the treatment of adolescents with psychoactive substance use disorders.