Purpose: To evaluate the clinical efficacy and safety of endostar combined with cisplatin/pemetrexed (CP) chemotherapy for elderly patients with advanced malignant pleural effusion (MPE) of lung adenocarcinoma. Methods: A total of 128 lung adenocarcinoma patients with MPE were randomly divided into two groups. Patients in the treatment group were treated with pemetrexed 500 mg/m(2), i.v., d 1, cisplatin intracavitary administration with a total dose of 75 mg/m(2), d 2, 5 and 8, and endostar intracavitary administration 45 mg, d 1, 4 and 7. Patients in the control group were treated with chemotherapy alone (pemetrexed and cisplatin and mode of administration were the same as for the treatment group. Results: The effective rates (ER) of the treatment group and control group were 81.82 and 64.52%, respectively (x(2)=4.906, p=0.027). The MPE control rates (DCRs) were 93.94 and 79.03%, respectively (x(2)=6.168, p=0.013). The control rate of the treatment group was higher compared with the control group (p<0.05), especially during the first period when it was 54.55% (p=0.019); in addition, the recurrence rate was lower (9.68 vs 30.61%, p=0.005). Dyspnea, mood and overall health improved significantly in the treatment group patients. No statistically significant differences in side effects between the groups were noticed. Conclusion: Intracavity endostar combined with intracavitary and i.v. pemetrexed and cisplatin had a significant effect on advanced MPE of lung adenocarcinoma. In addition, the quality of life (QoL) was significantly improved and the side effects were tolerable.