Abstract: Objective: To compare the effectiveness and safety of zoledronic acid with pamidronate in advanced lung cancer patients with bone metastases. Methods: Forty- one patients with moderate to severe pain due to osteolytic metastases were assigned into a prospective, randomized,double- blind and double- dummy study. There were 21 patients in the experimental group who were treated with zoledronic acid (4mg/?), and there were 20 patients in the control group who were treated with pamidronate (60mg/?). The primary effective endpoints were pain scores (numerical rating scale,NRS), pain relief rates and additive analgetic. The secondary efficacy parameters were quality of life (QOL) and Karnofsky performance status (KPS). The vital signs and lab parameters were monitored. Results: Fourteen days after zoledronic acid or pamidronate infusion, NRS, QOL and KPS were significantly improved. Zoledronic acid significantly relieved pain compared with pamidronate (NRS:3.38 vs 4.55, P<0.05) at the end point. The pain relief rate was 61.9% for zoledronic acid and 50% for pamidronate (P>0.05). Morphine use was observed in one patient in the group receiving zoledronic acid and in three patients in the group receiving pamidronate. Zoledronic acid ameliorated QOL and KPS similarly to pamidronate. The infusion time of zoledronic acid was significantly shorter compared with pamidronate (15 min vs 4 hrs). Adverse effects occurred in one patient in the zoledronic acid group and in four patients in the pamidronate group. The most common adverse effects included fever, nausea and vomiting. Conclusions: Zoledronic acid was more effective than pamidronate in palliating pain in advanced lung cancer patients with bone metastases. Zoledronic acid also provided a distinct convenience because of the short infusion time of 15 min compared with 4 hours for pamidronate infusion. Zoledronic acid and pamidronate were tolerated equally well.