Men with prostate cancer are at high risk of developing bone metastases that can lead to clinically significant skeletal morbidity. Recently, a randomized, placebo-controlled, phase III trial in 422 men with hormone-refractory prostate cancer and bone metastases demonstrated that zoledronic acid (4 mg every 3 weeks) significantly reduced the incidence and onset of skeletal complications and provided significant long-term reductions in bone pain compared with placebo. Patients received zoledronic acid for a 15-month core phase, with the option to continue therapy for 9 more months on the extension phase. To evaluate the continuing benefit of long-term zoledronic acid therapy, retrospective exploratory analyses were conducted based on the incidence of skeletal-related events (SREs; defined as pathologic bone fracture, spinal cord compression, surgery or radiation therapy to bone, or change in antineoplastic therapy for bone pain) occurring only during the extension phase of this trial. Quality of life parameters included assessment with the Brief Pain Inventory. Similar to results reported for the 15-month core phase and the entire 24-month study, the 9-month extension phase demonstrated that zoledronic acid significantly reduced the percentage of patients with an SRE (P = 0.017), prolonged the median time to first SRE (P = 0.036), reduced the annual incidence of SREs by 52% (P = 0.016), and reduced the risk of SREs by 53% (P = 0.022) compared with placebo. Furthermore, zoledronic acid was safe and well tolerated. Therefore, zoledronic acid provides long-term continuing clinical benefit for men with prostate cancer and bone metastases and represents a new therapeutic option for this population.