Objective To evaluate the possible influence of zoledronic acid on intra-operative bleeding and recurrence of spinal giant cell tumor. Methods A prospective, observational clinical control study was conducted. The zoledronic acid group: patients received zoledronic acid 1 week before (4 mg) and 3 weeks after (4 mg) the surgery; after then 4 mg zoledronic acid was given every 4 weeks for 3 years after surgery or till the patients could not tolerate. The control group: patients received no zoledronic acid or bisphosphonate before and after operation. The intraoperative blood loss was recorded for all the patients and the patients were given an imaging follow-up every 6 months postoperatively to detect recurrence. Results A total of 53 patients were eligible for this study, including 28 for zoledronic acid group and 25 for control group. The average amount of bleeding was (1 594±847) mL (400-3 200 mL) for zoledronic acid group and (2 476±769) mL (800-4 000 mL) for the control group, showing significant difference between the two groups (P<0.05). No patients in the zoledronic acid group had recurrence or severe adverse reactions within 3 years after surgery. Four patients (16%) in the control group had local recurrence within 3 years after surgery (2 patients occurred after 24 months, 2 patients occurred after 36 months). The Chi-square tests result showed significant difference in recurrence rates between the two groups (χ2=4.846,P=0.028). Conclusion Preoperative use of zoledronic acid can effectively inhibit the bleeding during the operation for spinal giant cell tumor, and long-term postoperative use of zoledronic acid can help to prevent recurrence, which needs large sample study for further verification.