Abstract: Objective : To evaluate the safety and efficacy of zoledronic acid i. v . as a single-drip therapy for treatment of the pain of osteolytic osseous metastases in patients with malignancy, with pamidronate disodium iv as the controls. Methods : A multicentral, prospective, randomized, double-blind and positive -controlled trial was carried out. A total of 205 patients with osteolytic osseous metastasis of malignancy with moderate to severe bone pain, confirmed by radiography or CT, took part in the study, and all of them have signed the written informed consent. 103 cases in the treatment group (zoledronic acid for injection, group A); 102 cases in the control group (pamidronate disodium for injection, group B). All of the results were evaluated during the 14 days after the single administration. Results : The ITT population included 204 cases, both of groups A and B had 102 cases. The median response duration was 4.98 ± 3.85 days and 4.68 ± 3.68 days respectively. The efficacy of the two groups in the treatment of pain during the administration duration over 14 days was compared: The response rate was 80.39T in group A, with 14.71% (15/102) CR and 65.69T (67/102) PR while the response rate was 79.41% in group B, with 14.71% (15/102) CR and 62.75% (64/102) PR. There was no significant difference between the two groups ( P>0.05). Conclusions : Change of bone pain scores in the patients with osteolytic osseous metastases in both groups demonstrate a significant reduction from baseline (P>0.05) ; Both the pain relief rate and the quality of life have been improved, and have differed significantly from baseline in both groups (P<0.01), but there is no significant difference between the two groups (P>0.05). The incidence of adverse effects is 33.33% in treatment group and 28.43% in control group.The major adverse effects include fever, headache, fatigue, nausea and skeletal pain. All of the adverse effects are mild, and no intervention is involved. There is no significant difference in the incidence of adverse effect of the two groups (P>0.05).