Abstract: Objective To compare the efficiency and toxicity of different chemotherapy regimens in treating advanced lung adenocarcinoma patients, to analyze the factors affecting drug efficacy and survival of patients, thus to provide better options for clinical treatment of advanced lung adenocarcinoma patients. Methods We reviewed and analyzed the clinical data of 141 hospitalized patients who were diagnosed pathologically as phase ⅢB or Ⅳ lung adenocarcinoma and treated initially. The patients were separated into three groups: Pemetrexed+Nedaplatin group, Pemetrexed+Cisplatin/Carboplatin group and New agent+Cisplatin/ Carboplatin group. After the treatment, we compared the efficiency and toxicity of different chemotherapy regimens, and the factors affecting drug efficacy and survival of patients. Results (1) Drug effects: objective response rates(ORR) of three groups were 35%, 25% and 18.52%; disease control rates(DCR) were 90%, 82.5% and 85.19%, without statistical significance(P>0.05); (2) Influence factors for efficiency of different treatment: The factors: gender, age, smoking history, and with or without chronic diseases, the number of metastasis organs, with or without brain metastasis, didn't affect DCRs of three groups; subgroups analysis showed that DCRs among either the three groups or Pemetrexed+Nedaplain groups made no statistical significance. EGFR wild patients who were treated with Pemetrexed and Platinum had ORR of 28.57% and DCR of 78.58%. The mutation group's ORR and DCR were 30.77% and 80.77%, without statistical significance(P>0.05). (3) Adverse events: Pemetrexed+Nedaplatin group had lower incidence of white blood cell reduction than the other two groups(P=0.007). (4) Survival analysis: The three groups' median progression-free survivals(PFS) were 8, 5 and 7 months. The PFS between each two groups had statistical significance(P<0.05). Conclusion Pemetrexed+Nedaplatin, as the first-line therapy for advanced lung adenocarcinoma patients, has higher ORR and DCR tendency, longer PFS and lower incidence of adverse event, especially in hematological toxicity. The factors: gender, age, smoker, the number of metastasis organs, with or without brain metastasis and with or without chronic disease, will not affect the effect of drugs. EGFR mutation patients have better effects tendency than wild ones who were treated with Pemetrexed and Platinum initially. Clinicians could take Pemetrexed+Nedaplatin as the first-line therapy for lung adenocarcinoma patients.