Medical settings provide opportunities for secondary prevention of traumatic stress and other sequelae of pediatric injury. This pilot randomized trial evaluated the delivery and effectiveness of a targeted preventive intervention based on best practice recommendations and integrated within acute medical care. Hospitalized injured children were screened for risk of developing posttraumatic stress disorder (PTSD). Those at risk (N = 85) were randomized to the intervention (n = 46) or usual care (n = 39). The preventive intervention did not reduce PTSD or depression severity or increase health-related quality of life, compared to usual care. Both groups improved over time, but 6 months postinjury approximately 10% of each group still met criteria for PTSD, suggesting room for improvement in comprehensive pediatric injury care.