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The current study identified subgroups of homeless youth and young adults that exhibited distinct co-occurring patterns of substance use and social stability (e.g., employment, school attendance, and housing), and evaluated the relative effectiveness of the Community Reinforcement Approach (CRA), Motivational Enhancement Therapy (MET), and case management (CM) in interrupting substance use and improving social stability. The differentiating effects of personal characteristics on the co-occurrence of substance use and social stability were also examined. Participants included 270 homeless youth and young adults who were randomly assigned to one of the three intervention conditions: CRA, n = 93, MET, n = 86, or CM, n = 91. Participants were assessed at baseline, 3, 6, and 12 months postbaseline. A dual trajectory latent class growth analysis identified four co-occurring patterns: low-stable substance use paired with low-increasing social stability, high-stable substance use paired with low-stable social stability, high-declining substance use paired with low-increasing social stability, and low-increasing substance use paired with high-stable social stability. Findings showed that CRA was superior in improving substance use and social stability simultaneously compared to MET and CM, and further, CM was more effective than MET. Personal factors including race, age, coping strategies, and behavior problems differentiated the co-occurring patterns of substance use and social stability. The findings underscore the significance in identifying subgroups of homeless youth that vary in problem severity in terms of their substance use and social stability, and offer evidence to help practitioners identify the most effective intervention that responds to the needs of homeless youth.