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Much of the large body of research on gender and related risk factors in adolescent substance use focuses on either normative community samples or high-risk, primarily male samples. Less attention has been given to substance use in high-risk female youth. A broader understanding of how gender impacts risk for substance use problems could aid in designing more appropriate interventions and policy. This seems particularly to be the case among females who have become involved in the justice system. In this study we analyze data from a sample of youth (N=421; 30% female; 66% nonwhite; mean age = 15 years, range = 11 to 18 years) referred by the justice system for mental health treatment. Youth completed treatment intake survey measures of mental health, substance use, general psychological functioning, and peer relations. Analyses show that gender moderates relations between individual and contextual risk factors and substance use outcomes. Specifically, males’ substance use was linked to both personal (e.g., beliefs about school) and contextual (e.g., parental knowledge as reported by parent) risk factors, whereas females’ substance use was sensitive only to contextual risk factors. Implications of these findings for research and practice with females in the justice system will be discussed.