Background: The aim of this study was to determine the efficacy and safety of loading-dose intravenous (i.v.) ibandronate in women with breast cancer and bone metastases. Patients and Methods: In this prospective, phase II, open-label study, 13 women with breast cancer, bone metastases, and moderate/severe bone pain received ibandronate 6 mg/day (i.v. loading-dose 15 min infusion over 3 consecutive days) with follow-up until day 14. Endpoints included pain response (primary), duration until pain response, analgesic use, Karnofsky index, safety (including hematologic, biochemical, and urine examinations), and adverse events. Results: Pain intensity decreased on days 7 and 14 versus day 1 (mean visual analogue scale score: 3.2 +/- 2.2 and 3.0 +/- 2.1 versus 6.1 +/- 0.9, respectively; p < 0.01 for both). Mean time to pain response was 8.2 +/- 3.3 days. Mean rate of analgesic use decreased (69.2%, 16.7% and 15.4% on days 1, 7 and 14, respectively). Mean Karnofsky index score increased (80.8 +/- 13.1 and 80.8 +/- 13.2, on days 7 and 14 versus 77.7 +/- 11.7 on day 1; p < 0.05 on both days). Conclusion: Bone pain and analgesic use decreased in women with breast cancer and bone metastases following loading-dose i.v. ibandronate which was well-tolerated with no renal safety concerns.