ABSTRACT: The integration of 12-Step philosophy and practices is common in adolescent substance use disorder (SUD) treatment programs, particularly in North America. However, although numerous experimental studies have tested 12-Step facilitation (TSF) treatments among adults, no studies have tested TSF-specific treatments for adolescents. We tested the efficacy of a novel integrated TSF.Explanatory, parallel-group, randomized clinical trial comparing 10 sessions of either motivational enhancement therapy/cognitive-behavioral therapy (MET/CBT; n = 30) or a novel integrated TSF (iTSF; n = 29), with follow-up assessments at 3, 6 and 9 months following treatment entry.Out-patient addiction clinic in the United States.Adolescents [n = 59; mean age = 16.8 (1.7) years; range = 14-21; 27% female; 78% white].The iTSF integrated 12-Step with motivational and cognitive-behavioral strategies, and was compared with state-of-the-art MET/CBT for SUD.Primary outcome: percentage days abstinent (PDA); secondary outcomes: 12-Step attendance, substance-related consequences, longest period of abstinence, proportion abstinent/mostly abstinent, psychiatric symptoms.Primary outcome: PDA was not significantly different across treatments [b = 0.08, 95% confidence interval (CI) = -0.08 to 0.24, P = 0.33; Bayes' factor = 0.28).during treatment, iTSF patients had substantially greater 12-Step attendance, but this advantage declined thereafter (b = -0.87; 95% CI = -1.67 to 0.07, P = 0.03). iTSF did show a significant advantage at all follow-up points for substance-related consequences (b = -0.42; 95% CI = -0.80 to -0.04, P < 0.05; effect size range d = 0.26-0.71). Other secondary outcomes did not differ significantly between treatments, but effect sizes tended to favor iTSF. Throughout the entire sample, greater 12-Step meeting attendance was associated significantly with longer abstinence during (r = 0.39, P = 0.008), and early following (r = 0.30, P = 0.049), treatment.Compared with motivational enhancement therapy/cognitive-behavioral therapy (MET/CBT), in terms of abstinence, a novel integrated 12-Step facilitation treatment for adolescent substance use disorder (iTSF) showed no greater benefits, but showed benefits in terms of 12-Step attendance and consequences. Given widespread use of combinations of 12-Step, MET and CBT in adolescent community out-patient settings in North America, iTSF may provide an integrated evidence-based option that is compatible with existing practices.