Background: Compared with open surgery, video-assisted thoracic surgery (VATS) has innovated the concept of the minimally invasive approach for non-small cell lung cancer (NSCLC) patients in past decades. This present study aimed to compare the perioperative and lymph node dissection outcomes between VATS lobectomy and open lobectomy for pathological stage T1 (pT1) NSCLC patients from both surgical and oncologic perspectives. Methods: This was a retrospective multicenter study. Patients who underwent surgical resection for pT1 NSCLC between January 2014 and September 2017 were retrospectively reviewed from 10 thoracic surgery centers in China. Perioperative and lymph node dissection outcomes of pT1 NSCLC patients who accepted VATS or open lobectomies were compared by propensity score matching (PSM) analysis. Results: Of the 11,360 patients who underwent surgery for pT1 NSCLC, 7,726 were enrolled based on the selection criteria, including 1,222 cases of open lobectomies and 6,504 cases of VATS lobectomies. PSM resulted in 1,184 cases of open lobectomies and 1,184 cases of VATS lobectomies being well matched by common prognostic variables, including age, sex, and surgical side. VATS lobectomy led to better perioperative outcomes, including less blood loss (133.5±200.1 vs. 233.3±318.4, P<0.001), lower blood transfusion rate (2.4% vs. 6.4%, P<0.001), shorter postoperative hospital stay (8.6±5.7 vs. 10.1±5.1, P<0.001), less chest drainage volume (1,109.5±854.0 vs. 1,324.1±948.8, P<0.001), and less postoperative complications (4.9% vs. 8.2%, P<0.001). However, open lobectomy had better lymph node dissection outcomes than VATS, with increased lymph node dissection numbers (16.1±9.4 vs. 13.7±7.7, P<0.001) and more positive lymph nodes being dissected (1.5±3.9 vs. 1.1±2.5, P=0.002). Compared with VATS, open lobectomy harvested more lymph node stations (5.5±1.9 vs. 5.2±1.8, P=0.001), including more pathological N2 (pN2) lymph node stations (3.4±1.4 vs. 3.1±1.3, P<0.001). Conclusions: VATS lobectomy was associated with better perioperative outcomes, such as less blood loss, lower blood transfusion rate, shorter postoperative hospital stay, less chest drainage volume and less postoperative complications. Open lobectomy has improved lymph node dissection outcomes, as more lymph nodes and positive lymph nodes were dissected for pT1 NSCLC patients during surgery. © 2021 Translational Lung Cancer Research.