Background: Rh-endostatin is a potent inhibitor of angiogenesis approved and widely used for advanced non-small cell lung cancer (NSCLC) in China. While the efficacy and safety of extended use of rh-endostatin with platinum-based chemotherapy during induced and maintenance therapy are still not very clear, and whether extended use of rh-endostatin can improve survival needs further investigation.Methods: We performed a retrospective analysis of chemotherapy-naive patients with stage IIIB-IV or recurrent NSCLC who had been treated with first-line chemotherapy plus rh-endostatin between January 2008 and June 2018. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Cox proportional hazards regression model was used to assess the prognostic importance of risk factors (age, gender, smoking status, Eastern Cooperative Oncology Group (ECOG) performance score, stage, pathology, previous thoracic surgery, and rh-endostatin treatment cycles).Results: A total of 105 patients, with a median of 4 cycles of chemotherapy with rh-endostatin, were eligible for analysis. The median (95% confidence interval (CI)) PFS and OS for patients with extended use of rh-endostatin (>_4 cycles) and nonextended use were 8.2 (4.2-12.3) vs. 3.2 (1.3-5.0) months [hazard ratio (HR) =0.50, P=0.002] and 25.1 (20.5-29.7) vs. 14.0 (9.2-18.8) months (HR =0.50, P=0.003), respectively. The objective response rate (ORR) and disease control rate (DCR) were 23.2% and 92.9%, respectively. Extended use of rh-endostatin (>_4 cycles) was significantly correlated with better PFS and OS in multivariate analysis. Patients with squamous cell cancers significantly benefited from the extended use of rh-endostatin (>_4 cycles) (n=56, P=0.001) but not adenocarcinoma (n=49, P=0.378). Hematologic and gastrointestinal toxicities occurred more frequently in the extended group compared with those in the nonextended group but without any significant differences.Conclusions: In patients with advanced NSCLC, the extended use of rh-endostatin (>_4 cycles) could provide additional survival benefits and satisfactory toxicity profiles, especially for those with squamous cell cancer, which merits further evaluation in a prospective randomized study in the future.