To investigate the clinical efficacy of combining digital subtraction angiography-guided percutaneous vertebroplasty (PVP) and I-125 seeds implantation for the treatment of spinal osteoplastic metastasis. A combination of PVP and I-125 implantation was conducted for 50 patients with spinal osteoplastic metastasis, while the other 50 patients who received regular radiation therapy were used as a comparison. Visual analogue pain scale (VAS) and score of life quality (EORTCQLQ-30) were determined for all the patients. Surgery was successful in 89 spinal segments of vertebral body in 50 patients. Each segment of vertebral body was injected with 1-5 mL (2.8 mL for thoracic and 3.1 mL for lumbar vertebral body on average) of bone cement. Postoperative X-ray and CT examination showed that all the patients in the PVP group achieved spinal stability. During the follow-up examination from 6 months to 5 years, 49 patients (98.0%) had significantly relieved back pain, and only 1 case (2.0%) had no obvious improvement. Postoperative VAS score and Karnofsky performance score (KPS) were significantly different from the preoperative scores (p < 0.05); and compared to the regular treatment group, PVP combined I-125 seeds showed much better clinical efficacy (p < 0.05). PVP is a minimally invasive treatment with easy operation and less complications. PVP can effectively relieve the pain, stabilize the spine, improve the life quality, and reduce the occurrence of paraplegia in patients with spinal osteoplastic metastasis. Utilization of I-125 seeds with PVP can enhance the clinical efficacy.