This article reports on effects of two earthquakes in Mexico on adolescents attending middle school. The earthquakes struck in close succession during the implementation of a school-based prevention program, providing an opportunity to assess emotional distress due to the earthquakes and whether the life skills taught in the program affected how students coped with the natural disaster. The objectives were to (1) evaluate the earthquakes' impact on students' distress; (2) assess if distress is associated with internalizing symptomology and externalizing behaviors; and (3) investigate if students receiving the original and adapted versions of the intervention coped better with the events. A Mexico-US research team culturally adapted "keepin' it REAL" to address connections between substance use among early adolescents in Mexico and exposure to violence. A random sample of public middle schools from three cities (Mexico City, Guadalajara, and Monterrey), stratified by whether they held morning or afternoon sessions, was selected. A total of 5522 7th grade students from 36 schools participated in the study. Students answered pretest and posttest questionnaires; the latter assessed earthquake-related distress and coping strategies. Earthquake-related distress was associated with all measures of undesired internalizing symptomology and externalizing behaviors. Compared to controls, students in the adapted intervention reported less aggressive and rule-breaking externalizing behavior and less violence perpetration. However, these intervention effects were not moderated by the level of earthquake-related distress, and they were not mediated by positive or negative coping. The findings have implications for prevention intervention research and policy as natural and human-made disasters occur more often.