OBJECTIVES: The objective of this study was to perform a model-based economic evaluation of denosumab vs. ZA in the prevention of SREs in patients with bone metastases from advanced solid tumors based on data from head to head phase III clinical trials in breast cancer (BrCa), prostate cancer (PrCa) and other solid tumors (OST), excluding multiple myeloma. METHODS: Three separate three-state Markov models (On Treatment, Off Treatment, and Dead) were developed for each cancer type. Constant SRE incidence rates estimated from the clinical trials were used for denosumab and ZA within each study. Overall survival was not significantly different between treatments, and was estimated using parametric distributions for extrapolation beyond the trial duration. Analyses were based on a lifetime model horizon and trial-based discontinuation.  SRE-related utility decrements were derived from trial-based EQ-5D data. SRE-related costs and administration cost were based on local data. Costs were discounted 4% and QALY outcomes at 1.5% according to local guidelines. The models predictions were validated by comparing the SRE predictions against those observed in the clinical trials. RESULTS: Denosumab resulted in fewer SREs, higher QALYs, lower SRE-related costs, lower administration cost and higher medication and total cost. The predicted incremental cost-effectiveness ratio (ICER) per SRE avoided was €1,644, €3,475, and €690 and the ICER per QALY gained was €26,524, €44,622, and €11,660 for BrCa, PrCa and OST, respectively. One-way sensitivity analyses were performed including administration cost, SRE and adverse event cost and SRE QALY decrements. Administration costs were important drivers of results.  CONCLUSIONS: Denosumab provides superior effectiveness vs. ZA with fewer SREs predicted over patients lifetime. The estimated incremental cost/QALY indicates that denosumab is cost-effective vsersus ZA in The Netherlands and represents good value for money in prevention of SREs in patients with bone metastases from all advanced solid tumors based on commonly accepted thresholds.