ABSTRACT. Objective: The aim of this study was to describe the prevalence and correlates of nonmedical prescription drug misuse (PDM) in a state population of youths in residential care for antisocial behavior. Method: Interviews assessing substance use, psychiatric symptoms, antisocial traits/behavior, and traumatic life experiences were conducted with 723 Missouri youths. Participants were predominantly male (87.0%), averaged 15.5 (SD = 1.2) years of age, and constituted 97.7% of the service population sampled. Results: Overall, 314 youths (43.4%) reported lifetime PDM; 33.7%, 32.0%, and 11.2% had misused prescription opioids, tranquilizers, and barbiturates, respectively. Prescription drug misusers were signifi cantly older, and larger proportions were girls, were White, and resided in small towns, compared with non-prescription drug misusers. Prescription drug misusers evidenced signifi cantly more varied, frequent, and problematic psychoactive drug use; evidenced higher levels of distressing psychiatric symptoms; and were nearly twice as likely to have been diagnosed with a psychiatric disorder, compared with non-prescription drug misusers. Traumatic life events, experiences of criminal victimization, and suicidal ideation were signifi cantly more prevalent in the histories of prescription drug misusers, compared with non-prescription drug misusers. In multiple logistic regression models, older age; White racial status; prior inhalant, marijuana, and LSD (lysergic acid diethylamide) use; residence in a small town; and impulsivity were associated with increased risk for PDM. Conclusions: Adolescents in residential care for antisocial behavior have high rates of PDM, as well as comorbid psychiatric and behavioral problems. Youths served in institutional settings should be routinely screened and treated for PDM and co-occurring disorders. (J. Stud. Alcohol Drugs, 71, 917-924, 2010)