Bone metastases occur in 30-40% of patients with advanced non-small cell lung cancer (NSCLC). Several studies have demonstrated the direct anticancer effect of zoledronic acid against lung cancer; however, most of these studies are preclinical research. A total of 311 NSCLC patients with bone metastases who were treated with zoledronic acid at Zhejiang Cancer Hospital between 2008 and 2011 were identified. Of these, 109 patients received zoledronic acid (4 mg intravenously every 21-28 days) more than 6 times (Group A), and the other 204 patients received zoledronic acid <6 times (Group B). All patients received standard chemotherapy and other treatments. Survival time was significantly longer in Group A than in Group B (385 vs. 275 days; P = 0.002), and the incidence of malignant pleural effusion was lower in Group A than in Group B (22.0 vs. 33.8%; P = 0.041). In conclusion, our study results suggest that a longer zoledronic acid treatment period had a better effect on survival. Zoledronic acid use might decrease the incidence of malignant pleural effusion.