OBJECTIVES: To evaluate the cost-effectiveness of denosumab compared to alendronate, zoledronic acid and no active osteoporosis treatment, for the treatment of post-menopausal osteoporosis (PMO) in elderly women aged 75 years and older in Sweden.   METHODS: A previously developed Markov cohort model was updated and used to estimate costs and effects, i.e. reductions in fracture occurrence, of denosumab vs. comparators in that elderly population. The model was populated with Swedish data on cost and fracture risks, and available clinical trial evidence on treatment fracture risk reduction for hip, vertebral and other fractures in an elderly population aged 75 years or older, where available. A life-time perspective was applied and analysis were performed both with the assumption that all patients stay on therapy for all 5 years and that some patients drop out of treatment over time (i.e. adjusting for imperfect treatment persistence). RESULTS: The base-case analysis showed that denosumab was cost-saving and more effective (i.e. dominant) versus all three comparators. The cost savings without adjustment for imperfect treatment persistence amounted to €4,500, €4,800 and €500 per patient, compared to no treatment, zoledronate and alendronate, respectively. Hip fracture is the most common fracture type in the elderly population, and denosumab treatment for 5 years avoided 140, 100 and 55 hip fractures per 1,000 treated patients, compared to no treatment, zoledronate and alendronate, respectively. Univariate and probabilistic sensitivity analyses showed that results were stable; denosumab dominated all comparators if consequences of imperfect treatment persistence were included or if comparator treatment costs were set to zero. CONCLUSIONS: Denosumab is a more cost-effective treatment alternative in an elderly PMO population. Compared to no treatment, zoledronic acid, and alendronate, denosumab can improve care in elderly PMO patients above 75 years and at the same time lower overall treatment costs in Sweden.