Oral ibandronate is a single-nitrogen bisphosphonate whose efficacy is similar to that of IV ibandronate for the treatment of bone metastases. The aim of this study was to compare the cost-effectiveness of oral ibandronate with zoledronic acid and generic pamidronate (both administered by IV) for the treatment of bone metastases in patients with breast cancer receiving oral hormonal therapy in the United Kingdom. A global economic model was adapted to the UK National Health Service. Patients were assumed to receive oral hormonal therapy for 50% of their projected 14.3-month survival. The primary outcome was incremental cost per quality-adjusted life-year (QALY). Bisphosphonate efficacy data for relative risk reduction of skeletal-related events (SREs) were obtained from clinical trials. Resource use data and costs associated with IV bisphosphonate infusions were derived from published studies and a unit cost database; monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with or without an SRE to adjust survival for quality of life. Therefore, differences in QALYs were driven by utility weights rather than survival time. Model design and inputs were validated through expert UK clinician review. The absence of comparative efficacy and safety data from clinical trials for the different bisphosphonates was a model limitation that we addressed by supporting our assumptions with UK expert clinician opinion and with expert clinician opinion outside of the United Kingdom, and by conducting sensitivity analyses. The projected total cost per patient was pound307 less with oral ibandronate compared with zoledronic acid, and pound158 less compared with the use of generic pamidronate (due to a reduction in staff time for infusions, avoidance of renal safety monitoring visits, and, in the case of IV generic pamidronate, a reduction in the number of SREs). Oral ibandronate was estimated to lead to a gain of 0.02 QALY, making it the economically dominant treatment option. In this study, we found that oral ibandronate was cost-effective for the management of bone metastases from breast cancer among patients receiving oral hormonal therapy in the United Kingdom. Oral ibandronate provided effective SRE and bone-pain management while avoiding resource use and costs associated with regular IV bisphosphonate infusions. Due to uncertainty surrounding the model assumptions, it would be valuable to repeat the analyses using data from comparative bisphosphonate trials, once they become available.