Abstract: Objective To study the value of video-assisted thoracoscopic surgery (VATS) and identify its indications in synthetic therapy for malignant pleural effusion secondary to non-small cell lung cancer. Methods A prospective randomized single-blinded controlled clinical trial was conducted. Fifty-three patients with moderate or large amount of ipsilateral malignant pleural effusion (MPE) secondary to non-small cell lung cancer (NSCLC) were randomly divided into VATS group and tube drainage group (TD group). All patients received chemotherapy with the regimen of paclitaxel combined with paraplatin, and the response rate of MPE after therapy, difference of Karnofsky performance status (KPS) grades before and after therapy and the survival rate of the patients were compared. Results The response rate of MPE after therapy in VATS group and TD group was 92.3% and 59.3%, and the complete remission rate was 88.5% and 44.4% (P<0.05), respectively. The difference of KPS grades before and after therapy in VATS group and TD group were 30 and 20, with a mean of 33.5±11.3 and 24.07±10.5 (P<0.05), respectively. Till August of 2005 years, all patients were available for followed-up, whose median survival time was 20 months in VATS group and 15 months in TD group. The 1-, 2- and 3-year survival rate were 65.4%, 38.5% and 22.4% in VATS group and 59.3%, 25.9% and 14.8% in TD group (P>0.05), respectively. Conclusion Video-assisted thoracoscopic pleurectomy can effectively control MPE and improve the quality of life for NSCLC patients with MPE, but failed to significantly improve the patietns’ survival rate in comparison with tube drainage. Except for grade Ⅳ, grades Ⅰ, Ⅱand Ⅲ according to CT findings all can be indications of VATS.