Abstract: Objective: To evaluate the clinical effect and safety profiles of zoledronic acid in the treatment of bone metastasis pain in cancer patients. Methods: A multicenter, double-blind and double-dim clinical trial on pamidronate was conducted in 237 cancer patients with bone metastasis pain from 12 centers in China. The patients were randomized into 2 groups, i.e., the experiment group and control group. Zoledronic acid (4 mg) was injected for 15 min in the experiment group and pamidronate (90 mg) i.v. within 4 h in the controls. The daily change of bone ache recorded by a visual analog scale (VAS) and the side effects were observed within 4 weeks as well. Results: The total 219 of 239 cases were eligible for final analysis, 112 from experimental group and 107 from control group were involved in the clinical response evluation. For the best clinical response within 14 days, after injection with those two biphosphanates, the complete response rate (CR rate), partial response rate (PR rate ) and clinical benefit rate was 10.08%, 53.78% and 90.75% respectively in the experiment group, compared with those data of 5.08%, 54.24% and 83.90% in the control group. There was no significant difference between the 2 groups. The daily clinical improvements of pain reduction and/or relief in the experiment group during the 5th, 7th till 12th day were absolutely better than those from the controls.There was no significant difference between the 2 groups for the consideration of pain improvement with 28 days . The medium maintain time (MMT) of complete response within 14 days were 5.51 and 3.01 days respectively between the 2 groups (P=0.0302), with the contrast of the MMT of effective responses (CR+PR) were 9.02 and 8.02 days (P>0.05). The incidence rate of the main side effects, like fever, hypocalcaemia, and fatigue was 23.94% and 27.98% respectively in the experiment group and the controls. No severe side effect was found in both groups. Conclusion: Zoledronic acid can effectively relieve bone metastasis pain. The response rate and side effect were similar to those of pamidronate.