OBJECTIVES: School-based health centers (SBHCs) provide health services to students at centers in pre-K–12schools or at off-site health facilities linked to schools. A recent Community Guide systematic review of effectiveness of SBHCs showed that SBHCs improved educational and health outcomes. Given the effectiveness and potential benefits of SBHCs, systematic assessment of their cost and benefit is important to examine the economic merits and evaluate the feasibility of implementing this intervention. The objective of this study was to conduct an economic evaluation of SBHCs using a systematic review. METHODS: Using economic systematic review methods developed for The Community Guide, 6,958 papers were identified for the search period January 1985 to September 2014. After two rounds of screening, 21 studies were included in this review: 15 studies reported on cost and 9 on benefit; three studies had both cost and benefit information. All expenditures in this review were presented in 2013 dollars. RESULTS: Intervention cost had two main components: start-up cost and operating cost. All but two of the cost studies reported operating cost only (ranged from $16,300 to $659,684 per SBHC annually). Benefits included healthcare cost averted and productivity and other loss averted. From the societal perspective, total annual benefit per SBHC ranged from $15,028 to $912,878. From healthcare payers’ perspective, particularly Medicaid, SBHCs led to net savings ranging from $30 to $969 per visit. From patients’ perspective, savings were also positive. Additionally, two benefit studies using regression analysis showed that Medicaid cost and hospitalization cost decreased with SBHCs. Finally, results from seven estimates in two cost–benefit studies showed that the societal benefit per SBHC exceeded intervention cost, with the benefit–cost ratio ranging from 1.38:1 to 3.05:1. CONCLUSIONS: The economic benefit of SBHCs exceeded the intervention operating cost. Further, SBHCs resulted in net savings to Medicaid.