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CONTEXT: Low-income and minority status in the United States are associated with poor educational outcomes, which, in turn, reduce the long-term health benefits of education. OBJECTIVE: This systematic review assessed the extent to which out-of-school-time academic (OSTA) programs for at-risk students, most of whom are from low-income and racial/ethnic minority families, can improve academic achievement. Because most OSTA programs serve low-income and ethnic/racial minority students, programs may improve health equity. DESIGN: Methods of the Guide to Community Preventive Services were used. An existing systematic review assessing the effects of OSTA programs on academic outcomes (Lauer et al 2006; search period 1985-2003) was supplemented with a Community Guide update (search period 2003-2011). MAIN OUTCOME MEASURE: Standardized mean difference. RESULTS: Thirty-two studies from the existing review and 25 studies from the update were combined and stratified by program focus (ie, reading-focused, math-focused, general academic programs, and programs with minimal academic focus). Focused programs were more effective than general or minimal academic programs. Reading-focused programs were effective only for students in grades K-3. There was insufficient evidence to determine effectiveness on behavioral outcomes and longer-term academic outcomes. CONCLUSIONS: OSTA programs, particularly focused programs, are effective in increasing academic achievement for at-risk students. Ongoing school and social environments that support learning and development may be essential to ensure the longer-term benefits of OSTA programs.