OBJECTIVES: The purpose of this study was to estimate the cost-effectiveness of multiple anti-osteoporotic drug therapies for secondary prevention of fractures in elderly women with osteoporosis in Japan. METHODS: A state transition model with nine health states (seven types of post-fracture, bedridden, and death) was developed to predict lifetime costs and quality-adjusted life years (QALY) of no anti-osteoporotic therapy and eight drug therapies in patients with a previous vertebral fracture. Incidence of hip, vertebral, and other fracture associated with age and bone mineral density (BMD) was estimated by using a regression approach based on epidemiologic studies in Japan. Comparative effectiveness of anti-osteoporotic drug therapies was derived from a published network meta-analysis. For the base-case analysis, we ran the model with T-score of -2.5 and different age (65, 70, and 75 years). Probabilistic sensitivity analysis was performed to assess parameter uncertainty. RESULTS: Alendronate therapy dominated all other strategies, resulting in 11.746 QALY and lifetime costs of $34,568. Compared to no preventive therapy, alendronate conferred an additional 0.458 QALY and saved lifetime costs of $13,753. Risedronate was equally cost-effective, resulting in 11.731 QALY and costs of $34,932. Applying a willingness to pay threshold of $50,000 per QALY, the probability of being cost-effective were estimated to 76.2 % and 23.8% for alendronate and risedronate, respectively. These results did not change in women aged 70 and 75 years. CONCLUSIONS: Bisphosphonate therapies for secondary prevention of fractures in elderly women would be cost-effective in terms of Japan healthcare system.