Although research has shown fade-out of the cognitive benefits of classroom-based preschool interventions, less is known regarding the durability of social-emotional impacts. This study examines the extent to which the multicomponent Chicago School Readiness Project (CSRP) intervention lowered risk of internalizing, externalizing, attention, and social difficulties from Head Start through elementary school for 602 low-income children. Results suggest that most children in this sample showed few social-emotional difficulties over time. However, one quarter of the sample exhibited profiles of transitory or building difficulties over six years. Random assignment to the CSRP preschool intervention significantly reduced children's odds of transitory attention and social difficulties in middle childhood, with preliminary evidence suggesting stronger impacts for children attending elementary schools characterized by low academic rigor and high neighborhood crime. CSRP was not found to be effective in preventing more robust, increasing forms of difficulty in the externalizing and attention domains. Implications for early childhood intervention and policy are discussed.