OBJECTIVES: Intravenous (IV) bisphosphonates reduce skeletal related events (SREs) and alleviate bone pain in patients with breast cancer and bone metastases (BCBM). However, these agents differ in terms of efficacy, administration time and costs. We compared the cost-effectiveness of IV bisphosphonates from a German inpatient perspective. METHODS: A 7-year literature-based model was designed to simulate the natural history, costs and quality-adjusted life expectancy (QALE) of 4 hypothetical cohorts of BCBM patients receiving no treatment (NT) or monthly IV ibandronate (IB), pamidronate (PA) or zoledronic acid (ZA). The model included probabilities of death and disease progression and the risk of SREs. The risk reduction in SREs with each bisphosphonate was estimated using the Andersen Gill hazard ratio v. NT (0.71 for IB, 0.70 for PA, and 0.56 for ZA). The model included direct medical costs for drugs, IV administration and SREs. Survival was adjusted for the time spent with and without SREs and on and off therapy to capture the bisphosphonates' impact on QALE. All outcomes were discounted at 5% per annum. RESULTS: The cumulative number of SREs over the 7-year simulation was lowest for ZA (3.53 per patient), followed by PA (4.17), IB (4.21) and NT (5.80). Average QALE was highest with ZA (1.10), followed by PA (1.09), IB (1.09) and NT (0.92). Total per-patient costs were lowest for ZA (€15,520), followed by PA (€16,968), NT (€17,317) and IBN (€17,881). In probabilistic sensitivity analyses, the 95th percentile value for the cost per QALY saved was €15,600 (ZA), €84,000 (IB), and €87,500 (PA). ZA, PA and IB were cost savings vs. NT in 79%, 56%, and 36% of model runs, respectively. CONCLUSIONS: For the management of BCBM patients, ZA is the preferred bisphosphonate as it is more effective and less expensive than other IV agents or even no therapy.