OBJECTIVE: IV bisphosphonates are effective in reducing skeletal related events (SREs) and alleviating bone pain in breast cancer patients with bone metastasis. However, these agents are characterized by different efficacy, administration time, and costs. Formal analyses are therefore needed to understand their overall economic value and budgetary impacts. We conducted a formal economic analysis to compare the budgetary impacts of these agents, from the UK NHS perspective. METHODS: A Markov model was developed to simulate over a period of seven years the survival and incidence of SREs for a hypothetical cohort of 1000 patients receiving no treatment (NT) or monthly injections of ibandronate (IBN), generic pamidronate (PA) or zoledronic acid (ZA). Probabilities of SREs (extrapolated from skeletal morbidity rates [SMR]) were obtained from published clinical trials of each agent. Costs of drugs and their infusion and cost of SREs were estimated from published sources. Survival was identical across all groups (25 months). RESULTS: Based on relative reduction of risk of SREs (ratio of SMR of bisphosphonate therapy vs. no therapy), the cumulative number of SREs over the lifetime of the patients was lowest for ZA (3820 events), followed by PA (4430), IBN (4890), and NT (6020). Total discounted costs (which included drug costs, infusion administration costs, and cost of treating SREs) for the cohorts of 1,000 patients were £2,457,000 lower for ZA than IBN, £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. ZA was less costly and more effective than all other treatment options, and is therefore the economically preferred option. CONCLUSIONS: Zoledronic acid appears to be the most cost-effective and least costly IV bisphosphonate therapy.