OBJECTIVES: Bone is the most common site for metastasis in cancer and bone metastases (BM) result in considerable morbidity and complex demands on health care resources. Bisphosphonates have been shown to treat and reduce skeletal-related events (SREs), which reduce quality-of-life and increase the risk of death. The aim of this study was to evaluate the cost-effectiveness of clodronate and zoledronate in the prevention of SREs in patients with BM. METHODS: We developed a Markov model to represent a cohort of patients diagnosed with BM in order to determine the cost-effectiveness of the studied therapeutic alternatives. The model has four health states: without SRE, with SRE (i.e., pathologic fracture, radiotherapy or surgery, and hypercalcemia), osteonecrosis and death. Transition probabilities came from SREs incidence rate meta-analysis previously performed by our group. Economical data were obtained from national data-bases. Univariate and multivariate sensibility analyses were used to determine the robustness of the pharmacoeconomic model. We used the public health perspective. Costs were presented in 2007 Brazilian Reais (1R$=1.60US$) RESULTS: BM treatment total cost in Brazil (on average, per patient) in five years (base case) was R$46,313 with clodronate and R$50,319 with zoledronate. Drug cost was the most influential item in the overall cost of BM treatment (>90%). In a five-year time-horizon, clodronate and zoledronate generated (on average, per patient) 2.00 and 1.90 QALYs, respectively. In this same time-horizon, clodronate and zoledronate also generated (on average, per patient) 1.81 and 1.76 SRE free-years, respectively. When we analyzed clodronate costs in relation to zolendronate per QALYs and SRE free-years produced, zolendronate was dominated by clodronate. Multivariate sensibility analysis did not show changes in the initial results of this pharmacoeconomic model CONCLUSIONS:From the Brazilian Ministry of Health perspective, clodronate was dominant in comparison to zoledronate in preventing SREs in patients with BM