OBJECTIVES: To evaluate the cost-effectiveness of bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), raloxifene, calcitonin and strontium ranelate, with a combination of calcium and Vitamin D as comparator, for the prevention of osteoporosis-related fractures in Thai post-menopausal women. METHODS: A Markov state transition model with 1-year cycle length was designed to simulate the cost-effectiveness of 7 osteoporosis treatment interventions, compared with calcium and vitamin D, in Thai post-menopausal women aged 50-70 years. The model health states were categorized as osteopenia/no fracture, hip fracture, vertebral fracture, post-hip fracture, post-vertebral fracture and death. Treatment effects were obtained from published literature. The analysis was conducted using a societal perspective and included direct medical, direct non-medical and indirect costs. Uncertainty was investigated by a probabilistic Monte Carlo simulation. Treatment outcomes were measured in terms of number of fractures avoided, number of life years gained and quality-adjusted life years (QALY) gained. Cost-effectiveness was defined as an ICER of less than 300,000 Baht (an incremental cost of ≤300,000 Baht for an outcome of no fracture for 1 year). RESULTS: 1) For patients with no prior fracture (primary prevention), zoledronic acid is cost-effective at ≥65 years, alendronate, risedronate and ibandronate at ≥70 years  2) For patients with prior vertebral fracture (secondary prevention), zoledronic acid is cost-effective at ≥50 years, alendronate, risedronate and ibandronate at ≥55 years, raloxifene and strontium ranelate at ≥60 years; 3) For patients with prior non-vertebral fractures, zoledronic acid is cost-effective at ≥60 years, alendronate at ≥65 years, and risedronate and ibandronate at ≥70 years. CONCLUSIONS: Zoledronic acid, followed by other bisphosphonates, is the most cost-effective treatment option for both primary and secondary fracture prevention in Thai post-menopausal women with osteoporosis. These findings should be implemented in the government policy for selecting appropriate anti-osteoporotic drugs and reimbursement support strategy for Thai postmenopausal women with osteoporosis.