Background: Pemetrexed continuation maintenance therapy has been increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this treatment strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in EGFR-negative lung adenocarcinoma. Methods: A total of 114 patients with EGFR-negative lung adenocarcinoma who were treated with platinum-based doublet between January 2010 and July 2015 were retrospectively enrolled for this study. Response to treatment and survival according to different treatment strategy were analyzed and compared. Results: Thirty four patients received pemetrexed continuation maintenance chemotherapy and 80 received conventional platinum- based doublet without maintenance chemotherapy. Median progression-free survival (PFS) was significantly higher in the pemetrexed maintenance group compared to conventional chemotherapy group (p ＜ 0.01). In addition, median overall survival (OS) was also significantly higher in the pemetrexed maintenance group (23.3 vs 17.0 months, p = 0.005). Multivariate analyses showed that the use of pemetrexed maintenance chemotherapy was associated with improved PFS and OS (Hazard ratio 0.81 and 0.67, respectively). Conclusion: Premetrexed continuation maintenance treatment has a survival benefit compared to conventional platinum-based chemotherapy for patients with EGFR-negative advanced lung adenocarcinoma. Large-scale studies are needed to confirm our findings.