Background: Relatively few studies have examined prevalence and predictors of posttraumatic stress disorder (PTSD) or major depressive episode (MDE) in disaster-affected adolescents. Fewer still have administered diagnostic measures or studied samples exposed to tornadoes, a common type of disaster. Further, methodologic problems limit the generalizability of previous findings. This study addressed prevalence estimates and risk factors for PTSD and MDE among adolescents exposed to the Spring 2011 tornado outbreak in Alabama and Joplin, Missouri. Methods: A large (N = 2000), population-based sample of adolescents and caregivers, recruited randomly from tornado-affected communities, participated in structured telephone interviews. PTSD and MDE prevalence were estimated for the overall sample, by gender, and by age. Hierarchical logistic regression was used to identify risk factors for PTSD and MDE. Results: Overall, 6.7% of adolescents met diagnostic criteria for PTSD and 7.5% of adolescents met diagnostic criteria for MDE since the tornado. Girls were significantly more likely than boys to meet diagnostic criteria for MDE, and older adolescents were more likely than younger adolescents to report MDE since the tornado. Female gender, prior trauma exposure, and an injured family member were associated with greater risk for PTSD and MDE. Specific incident characteristics (loss of services, concern about others' safety) were associated with greater PTSD risk; prior disaster exposure was associated with lower MDE risk. Conclusions: However, most adolescents were resilient following tornado exposure, roughly 1 in 15 developed PTSD, 1 in 13 developed MDE, and many more endorsed subclinical mental health problems. Information regarding specific risk factors can guide early screening, prevention, and intervention efforts in disaster-affected communities.