Purpose: To assess retrospectively the efficacy and safety of percutaneous vertebroplasty (PVP) combined with zoledronic acid (ZA) for the treatment of painful osteolytic spinal metastases from breast cancer. Materials and Methods: PVP was performed in 43 patients with breast cancer and painful osteolytic spinal metastases; vertebrae were treated. The patients subsequently received 4 mg ZA via a 15-minute intravenous infusion every 4 weeks for 12 months. Pain and quality of life (QoL) were assessed using a visual analog scale (VAS) and Karnofsky performance scale (KPS), respectively, 24 hours before PVP and 24 hours, 1 month, 3 months, 6 months, and 12 months after PVP. Skeletal-related events (SREs) were assessed for 12 months following the intervention. Results: The mean VAS scores decreased significantly from 7.6 +/- 1.9 at 24 hours before PVP to 3.6 +/- 1.4 at 24 hours, 2.0 +/- 1.5 at 1 month, 2.8 +/- 1.6 at 3 months, 3.1 +/- 0.8 at 6 months, and 2.5 +/- 0.9 at 12 months after the intervention (P <. 05). KPS scores increased significantly after the combination treatment (P < .05). Compared with previous studies without PVP or ZA treatment, this patient group had a lower incidence of SREs. No major complications were observed. Conclusions: PVP combined with ZA was shown to be a highly effective and safe combination therapy to relieve pain and improve QoL, in patients with osteolytic spinal metastases from breast cancer. The combination therapy also prevented the occurrence Of SREs.