The effectiveness and economic efficiency of school-based scoliosis screening program (SSSP) remain controversial, particularly regarding the balance between benefits and harms related to inappropriate screening of adolescent idiopathic scoliosis (AIS). In South Korea, where healthcare reimbursement rates are exceptionally low, the cost-effectiveness of SSSP and its temporal trends have not been comprehensively evaluated. This population-based observational study aims to evaluate the temporal trends in the cost-effectiveness of a SSSP in South Korea from 2012 to 2023 within a low-reimbursement healthcare system. Based on the data of SSSP between 2012–2023 (n = 735,313), screening rates and the distribution of scoliosis severity were assessed to evaluate screening performance. Total costs associated with SSSP implementation and hospital referrals were calculated. All costs were converted to present values (PVs) by adjusting for the consumer price index and applying a discount rate. Cost-effectiveness was assessed using cost per diagnosed AIS case and cost per inappropriate screening event. Over the 10-year period, the PV of the cost required to diagnose one AIS patient was $66.54, whereas the PV associated with one inappropriate screening was $36.44. The PV of SSSP per screened individual decreased from $2.03 in 2012 to $1.36 in 2018, followed by an increase to $2.24 in 2023. In contrast, the PV of referral costs per individual steadily declined from $16.24 in 2012 to $8.12 in 2023. The inappropriate screening rate per $100 increased until 2018 (38.63), markedly declined through 2022 (13.68), and rose again in 2023 (23.35). Meanwhile, the scoliosis screening rate per $100 increased until 2021 (46.00) but sharply decreased thereafter, reaching 21.36 in 2023. Within a low-reimbursement healthcare system, the SSSP in South Korea demonstrates favorable cost-effectiveness at the population level. However, the persistently substantial proportion of inappropriate screenings indicates that further improvements in screening accuracy are necessary to enhance efficiency and optimize resource utilization. Advancements in screening tools and strategies may improve the overall cost-effectiveness of SSSP.