OBJECTIVE: Bisphosphonates inhibit bone resorption, reducing skeletal-related events (SREs) and bone pain in breast cancer patients with bone metastasis. These agents are characterized by different efficacy, safety, dosage form, time of administration, compliance, and acquisition costs. We developed formal budget impact model to guide the selection of bisphosphonate therapy from the perspective of the UK NHS. METHODS: We developed a Markov model to simulate over a period of seven years the the incidence of SREs and cost of care for a hypothetical cohort of 1000 patients receiving no treatment (NT), daily oral ibandronate (OI), or monthly injections of generic pamidronate (PA) or zoledronic acid (ZA). This literature-based model included assumptions about skeletal morbidity rates (SMR, directly obtained or extrapolated from placebo-controlled clinical trials), mortality, costs of drug (including infusion cost), cost of SRE, and compliance with therapy. Survival was assumed to be identical across all groups (25 months). RESULTS: Based on relative reductions of risk of SREs (ratio of SMR of bisphosphonate therapy vs. no therapy) and compliance with therapy, the cumulative number of SREs over the lifetime of a patient was projected to be lowest for ZA (3820 events), followed by PA (4430), OI (4910), and NT (6020). Total discounted costs (including drug, infusion administration costs, SRE treatment costs) for the cohorts of 1,000 patients were £1,949,000 lower for ZA than OI, £1,160,000 lower than PA, and £556,000 lower than NT. Fifty and 75% of these savings, respectively, occurred within the first 12 and 24 months of the simulation. These findings were robust across various sensitivity analyses. CONCLUSIONS: For breast cancer patients with bone metastasis, zoledronic acid appears to be the most cost-effective and least costly bisphosphonate therapy, even compared to no therapy.