OBJECTIVES: Zoledronic acid (ZOL) is efficacious in reducing skeletal-related events (SREs) due to bone metastases in RCC patients. However limited information is available on its cost-effectiveness. This study evaluated the economic impact of ZOL therapy for RCC patients in France, Germany, and the UK. METHODS: The source for this analysis was a retrospective evaluation of a 9-month trial comparing ZOL vs. placebo with concomitant antineoplastic treatment in RCC patients with bone metastases. A model was developed to simulate quality-adjusted life years (QALYs) and costs by integrating relevant assumptions and published information pertaining to SRE-incidence, costs, and effects on quality-of-life (QoL), mortality, drug and administration costs. It was assumed that patients experienced a 20 to 80% decrease in QoL for a month following an SRE, depending on the SRE type. SRE costs were based on diagnosis-related group (DRG) tariffs and the published literature. RESULTS: ZOL-treated patients (n=27) experienced 1.07 fewer SREs, gained discounted QALYs ( France and Germany=0.1563; the UK=0.1575), and incurred substantially lower discounted SRE-related costs ( France=–€4196, Germany=–€3880, the UK=–€3355) compared with patients who were on placebo (n=19). Inclusive of the treatment costs, ZOL savings per patient by country were as follows: France=€1358, Germany=€1223, and the UK=€719. According to probabilistic sensitivity analyses, ZOL therapy was predicted to result in cost savings in 67% to 77% of 1000 model simulations, depending on the country. The cost per QALY gained was below the threshold of €30,000 in approximately 93% of the cases across all countries. CONCLUSIONS: ZOL is a cost-saving therapy for bone health management of advanced RCC patients in France, Germany, or the UK. This is because ZOL effectively prevents SREs, improves patient QoL, incurs lower health-related costs, and offers a better economic utilization of healthcare resources relative to placebo.