Background: Spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) exhibits dual intraoperative and postoperative advantages for patients with non-small cell lung cancer (NSCLC).However, there is a lack of data regarding its long-term survival superiority over the double-lumen intubated mechanical ventilation video-assisted thoracoscopic surgery (MV-VATS) or thoracotomy.Methods: A retrospective study was conducted from 2011 to 2018 in the First Affiliated Hospital of Guangzhou Medical University among patients with NSCLC who underwent the SV-VATS or the MV-VATS. Patients receiving the SV-VATS were the study group, and patients receiving the MV-VATS were the control group. Propensity score matching (PSM) was performed to establish 1:1 SV-VATS versus MV-VATS group matching to balance potential baseline confounding factors. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints were perioperative outcomes. The baseline information of these patients was recorded. The perioperative data and survival data were collected using a combination of electronic data record system and telephone interview. A 1:1:1 SPM was also used to compare the OS in the SV-VATS, the MV-VATS and thoracotomy group by using another database, including patients undergoing thoracotomy and the MV-VATS.Results: For the two-group comparison, after 1:1 PSM, a matched cohort with 400 (200:200) patients was generated. The median follow-up time in this cohort was 4.78 years (IQR, 3.78-6.62 years). The OS (HR =0.567, 95% CI, 0.330 to 0.974, P=0.0498) and the DFS (HR =0.546, 95% CI, 0.346 to 0.863, P=0.013) of the SV-VATS group were significantly better than the MV-VATS group. There were no statistically differences between the SV-VATS and the MV-VATS group on the operative time (158.56±40.09 vs.