To use cluster analysis to determine profiles of adolescents at risk for HIV. Methods Adolescents 15โ21 years old (N = 1153) with a history of unprotected sex were assessed in five domains of risk (unprotected sex, alcohol/marijuana use, other drug use, mental health crises, and arrest/school dropout) as well as demographic, contextual, and behavioral variables. Results Cluster analysis revealed separate three-cluster solutions for males and females. Among males, clusters were characterized by (a) mental health crises and unprotected sex, (b) alcohol/marijuana use and unprotected sex, and (c) lower risk. Among females, clusters were distinguished by (a) unprotected sex, (b) substance use and mental health crises, and (c) lower risk. Cluster membership was associated with secondary variables related to sexual risk. Conclusions Even within populations of high-risk adolescents, subgroups exist for which specific risk factors co-occur, particularly unprotected sex, mental health crises, and substance use. These patterns suggest that effective HIV prevention interventions may need to target the association between mental health and/or substance abuse with sexual risk for some adolescents