OBJECTIVES: Zoledronic acid (ZOL) is the only bisphosphonate indicated for preventing skeletal-related events (SREs) in patients with bone metastases from prostate cancer (PC). We estimated and compared the cost-effectiveness of ZOL versus placebo for this indication in France, Germany, Portugal, and the Netherlands. METHODS: Incremental costs and quality-adjusted life-years (QALYs) associated with ZOL and placebo were estimated using a literature-based decision analytic model using data from a 15-month randomized trial comparing ZOL (4 mg monthly; n=214) with placebo (n=208). The model included assumptions about SREs, mortality, drug and administration costs, SRE costs, quality of life, and therapy duration. SRE costs were estimated using Diagnosis Related Group tariff information (supplemented with published literature) in France and Germany, and published retrospective medical record review cost analyses in Portugal and the Netherlands. RESULTS: Over 15 months, the cumulative projected SREs were 0.83 for ZOL and 1.66 for placebo. ZOL reduced SRE costs by €2659 to €4005, depending on the country. SRE cost savings were greatest in the Netherlands, followed by Portugal, Germany, and France. ZOL reduced total costs (including drug costs) by €62 in Portugal and €301 in the Netherlands, but increased costs by €562 in Germany and €1022 in France versus placebo. ZOL increased quality-adjusted survival by 0.03566 QALY per patient, with an incremental cost per QALY gained versus placebo of €15,770 in Germany and €28,648 in France. In all countries, the cost-effectiveness ratio for ZOL was favorable and substantially below the internationally accepted €50,000/QALY threshold. Costs and QALYs were saved with ZOL in Portugal and the Netherlands. CONCLUSIONS: In patients with bone metastasis from PC, ZOL is economically attractive. The cost-effectiveness ratio for ZOL is below standard cost-effectiveness thresholds used by most healthcare systems. In Portugal and the Netherlands, ZOL is cost-saving versus placebo.