We report on a randomized controlled trial of Targeted Mental Health in Schools (TaMHS), which is a nationally mandated school-based mental health program in England. TaMHS aimed to improve mental health for students with, or at risk of, behavioral and emotional difficulties by providing evidence-informed interventions relating to closer working relationships between health and education services. Our study involved 8,480 children (aged 8-9 years) from 266 elementary schools. Students in intervention schools with, or at risk of, behavioral difficulties reported significant reductions in behavioral difficulties compared with control school students, but no such difference was found for students with, or at risk of, emotional difficulties. Implementation of TaMHS was associated with increased school provision of a range of interventions and enhanced collaboration between schools and local specialist mental health providers. The implications of these findings are discussed, in addition to the strengths and limitations of the study.