This study examines the effect of drug treatment on reducing HIV-related risky sex behavior among 796 adolescents entering drug treatment programs in four cities in the United States. More than half of the adolescents (54%) reported reductions in risky sex behavior after treatment. Conduct-disordered adolescents with abuse history, unmet physical and emotional needs, and low commitment to school were associated with lack of improvement. Furthermore, conduct-disordered adolescents who perceived treatment to be effective were more likely to show posttreatment improvement, with the exceptions that those who scored high on hostility or low in self-perception were not likely to improve. Among adolescents without conduct disorder, receipt of mental health services was associated with improvements in their risky sex behavior. The effect of drug treatment on HIV risk reduction can be increased when attention is focused on adolescents’ pretreatment risk factors, service needs, intreatment responses, and key personality characteristics.