Background: Building on previous research with adolescents that examined demographic variables and other forms of substance abuse in relation to non-medical use of prescription drugs (NMUPD), the current study examined potentially traumatic events, depression, posttraumatic stress disorder (PTSD), other substance use, and delinquent behavior as potential correlates of past-year non-medical use of prescription drugs. Method: A nationally representative sample of 3,614 non-institutionalized, civilian, English-speaking adolescents (aged 12-17 years) residing in households with a telephone was selected. Demographic characteristics, traumatic event history, mental health, and substance abuse variables were assessed. NMUPD was assessed by asking if, in the past year, participants had used a prescription drug in a non-medical manner. Multivariable logistic regressions were conducted for each theoretically derived predictor set. Significant predictors from each set were then entered into a final multivariable logistic regression to determine significant predictors of past-year NMUPD. Results: NMUPD was endorsed by 6.7% of the sample (n = 242). The final multivariable model showed that lifetime history of delinquent behavior, other forms of substance use/abuse, history of witnessed violence, and lifetime history of PTSD were significantly associated with increased likelihood of NMUPD. Conclusions: Risk reduction efforts targeting NMUPD among adolescents who have witnessed significant violence, endorsed abuse of other substances and delinquent behavior, and/or endorsed PTSD are warranted. Interventions for adolescents with history of violence exposure or PTSD, or those adjudicated for delinquent behavior, should include treatment or prevention modules that specifically address NMUPD.