OBJECTIVE: To assess the cost-effectiveness of a single intravenous dose of zoledronic acid 5 mg (ZOL) compared to a daily regimen of oral risedronate 30 mg (RIS) over 2 months in the long-term (2-year) management of Paget's disease of the bone (PDB) in Germany. METHODS: A model-based incremental cost-effectiveness analysis was conducted over four half-year cycles. Clinical efficacy was reflected in four health states: response, non-response, relapse, no-relapse. Response was defined as normalization of the serum alkaline phosphatase (SAP) value after 6 months. Relapse was defined as an increase in SAP of at least 50% from the value at 6 months and at least 1.25 times the upper normal limit. Retreatment was assumed in case of non-response or relapse. Efficacy data were obtained from two 6-month randomized clinical trials which compared ZOL with RIS in patients with PDB. Relapse data were obtained from the extended observation phase of the trial, in which SAP was measured at 6-monthly intervals to determine whether patients were still in response. The analysis was conducted from the German payers' perspective. Only direct healthcare costs such as those for physician visits, SAP measurement and drug administration were considered. Cost data were derived from published sources for the year 2006. Costs and effects in the second year were discounted by 5%. A probabilistic sensitivity analysis (PSA) was performed to investigate the robustness of the results. RESULTS: Due to more responders and longer remission, treatment with ZOL resulted in an incremental of 6.2 months in response and a cost saving of 243 € over 2 years compared to RIS. The results of the PSA indicated that ZOL was more effective and cost-saving with 100% certainty. CONCLUSION: ZOL presents a dominant treatment option in the long-term management of PDB indicating superior effectiveness at a lower cost.