OBJECTIVES: To evaluate the cost-effectiveness of denosumab compared to supportive care (no active osteoporosis treatment), alendronate, ibandronate, risendronate and strontium ranelate for the treatment of women with post-menopausal osteoporosis (PMO) in Greece. METHODS: An 8-state, 6-month cycle Markov cohort model was developed in order to estimate costs and effects, i.e. reductions in fracture occurrence, of denosumab vs. comparators for a 5year period, from a third-party payer perspective (Euros, 2011). The model was populated according to the characteristics of the FREEDOM clinical trial population (mean age: 72.3, prevalence of vertebral fracture: 23.6%, femoral neck T-score ≤-2.5), that also provided the data on efficacy of denosumab. Data on efficacy (relative risk of fractures) for the comparators were taken from a published meta-analysis. The model took into account treatment persistence across all comparators, as well as a 2year residual effect of treatment after discontinuation. RESULTS: The base-case analysis showed that the incremental cost per QALY gained with denosumab was €18,813, €24,784, €13,727, €18,436 and €11,114 versus no treatment, alendronate, ibandronate, risendronate and strontium ranelate, respectively. The probabilistic sensitivity analysis demonstrated that denosumab was cost-effective in an implicit €30,000 threshold for 81.6% of the iterations versus no treatment and risendronate, 63.4% versus no treatment and alendronate and 88.2% versus no treatment and ibandronate. Univariate sensitivity analyses showed that changes in persistence rates, baseline age and T-score where the factors with the most significant influence in the results. CONCLUSIONS: In a disease that entails a significant morbidity and socioeconomic burden, denosumab seems to be a cost-effective alternative to established treatment regimens for osteoporosis in Greece.