The present study aimed to utilize a Receiver Operating Characteristic (ROC) approach in order to improve clinical decision-making for adolescents at risk for the development of psychopathology in the aftermath of a natural disaster. Specifically we assessed theoretically-driven individual, interpersonal, and event-related vulnerability factors to determine which indices were most accurate in forecasting PTSD. Furthermore, we aimed to translate these etiological findings by identifying clinical cut-off recommendations for relevant vulnerability factors. Our study consisted of structured phone-based clinical interviews with 2,000 adolescent-parent dyads living within a 5-mile radius of tornados that devastated Joplin, MO, and northern Alabama in Spring 2011. Demographics, tornado incident characteristics, prior trauma, mental health, and family support and conflict were assessed. A subset of youth completed two behavioral assessment tasks online to assess distress tolerance and risk taking behavior. ROC analyses indicated four variables that significantly improved PTSD diagnostic efficiency: Lifetime depression (AUC=.90), trauma history (AUC=.76), social support (AUC=.70), and family conflict (AUC=.72). Youth were 2–3 times more likely to have PTSD if they had elevated scores on any of these variables. Of note, event-related characteristics (e.g., property damage) were not related to PTSD diagnostic status. The present study adds to the literature by making specific recommendations for empirically-based, efficient disaster-related PTSD assessment for adolescents following a natural disaster. Implications for practice and future trauma-related developmental psychopathology research are discussed.