Living in poverty increases exposure to adversities that undermine healthy development, impeding growth in the social-emotional and language skills that support adaptive coping and promote mental health. Evidence-based programs have the potential to improve current preschool practice and strengthen these early skills, potentially reducing risk for later psychopathology. The authors tested the hypothesis that an enrichment program in preschool would be associated with reduced levels of psychopathology symptoms at the transition from middle to secondary school.The Head Start REDI (Research-Based, Developmentally Informed) intervention was used to enrich preschool classrooms serving children from low-income families with an evidence-based social-emotional learning (SEL) program and a coordinated interactive reading program. Centers were randomly assigned to the intervention or usual practice, and 356 4-year-olds (58% White, 25% Black, 17% Latino; 54% female) were followed into early adolescence. Hierarchical linear models were used to evaluate intervention effects on teacher-rated psychopathology symptoms using the Strengths and Difficulties Questionnaire in grade 7 (ages 12-13) and grade 9 (ages 14-15), 8-10 years after the end of the intervention.Statistically significant intervention-related reductions were observed in conduct problems and emotional symptoms in the intervention group. In addition, the proportion of youths with clinically significant levels of conduct problems, emotional symptoms, and peer problems was reduced in the intervention group, with rates one-third of those in the control group.The study findings indicate that enriching preschool programs serving at-risk children with a relatively inexpensive evidence-based SEL program with interactive reading substantially improved the later benefits for adolescent emotional and behavioral health. This kind of SEL enrichment represents an approach that can leverage public investments in preschool programs to enhance public health.