Background: A school-based obesity prevention study (Medical College of Georgia FitKid Project) started in the fall of 2003 in 18 elementary schools. Half of the schools were randomized to an after-school program that included moderate-to-vigorous physical activity, healthy snacks, homework assistance, and academic enrichment. All third graders were invited to enroll. The objective of this study was to assess the cost-effectiveness (CE) of the first-year intervention. Methods: Standard CE analysis methods and a societal perspective were used. Program delivery costs incurred during the first-year intervention and the usual after-school care costs that would occur in the absence of the intervention were estimated (in 2003 dollars). Net intervention costs were calculated by subtracting the usual after-school care costs from the intervention costs. The effectiveness of the intervention was measured as percent body fat (%BF) reduction compared with a control condition. The CE was assessed as the net intervention cost divided by the effectiveness of the intervention. Results: The intervention costs totaled $174,070, $558/student, or $956/student who attended greater than or equal to 40% of the intervention sessions. The usual after-school care costs were estimated at $639/student. Students who attended greater than or equal to 40% of the intervention reduced %BF by 0.76% (95% confidence interval: -1.42 to -0.09) at an additional cost of $317/student. Conclusions: Subjects who attended greater than or equal to 40% of the intervention achieved a significant reduction in %BF at a relatively low cost. School-based obesity prevention programs of this type are likely to be a cost-effective use of public funds and warrant careful consideration by policy makers and program planners. (Contains 3 tables.)