OBJECTIVES: Zoledronic acid (ZOL) is the only approved bisphosphonate for SRE prevention in hormone-refractory prostate cancer (mHRPC). However, in the United Kingdom (UK), 19% and 4% of metastatic, mHRPC patients, do not receive bisphosphonates or receive non-approved/unproven bisphosphonates (i.e., pamidronate [PAM]), respectively for the prevention of skeletal-related events (SREs). This analysis sought to estimate, from a UK payer perspective, the cost effectiveness of providing ZOL to those mHRPC patients not receiving ZOL.   METHODS: This analysis was based on the results of a published randomized phase III clinical trial wherein mHRPC patients received ≤15 months of ZOL or placebo (PBO) (Saad et al, 2002). Since PAM has been shown to be no different than PBO in mHRPC in a pooled analysis of two trials (Small et al 2003) (i.e., 25% of subjects experienced an SRE at 6 months), the PBO cohort data from the ZOL trial was as a surrogate for PAM data in the absence of a direct comparison of ZOL versus PAM (or other bisphosphonates). Costs were estimated using hospital tariffs and published/internet sources. Quality adjusted life years (QALYs) gained were based on a previously published analysis of the Saad et al (2002) data. Survival was assumed to be identical for both groups.   RESULTS: Compared with the use of PAM/PBO, treatment with ZOL (at list price of £174.14/infusion vs £80/infusion with PAM) resulted in increased QALYs (+0.03566/pt), fewer SREs (-0.8314/pt, i.e., 0.8315 vs 1.6629), and fewer SRE-related costs (-£1,639/pt, i.e., £2,004 vs. £3,643). Total costs were higher with ZOL (+£702/pt). ZOL cost £19,689/QALY.   CONCLUSIONS: The use of ZOL for the prevention of SREs in UK patients with bone metastases secondary to mHRPC is cost effective relative to providing no or unapproved bisphosphonates.