ObjectiveTo compare and analyze clinical effects of video-assisted thoracoscopic surgery (VATS) lobectomy and systematic lymph node harvests for peripheral non-small cell lung cancer (PNSCLC) patients between single-port (SP) and multi-port (MP) with a propensity-matched analysis. MethodsWe retrospectively analyzed the clinical data of 324 patients presented with PNSCLC and admitted in the Affiliated Hospital of Qingdao University from January 2013 through December 2015. Six-eight patients underwent single-port thoracoscopic lobectomy were as a SP group and 256 patients with multi-port thoracoscopic lobectomy. Another 68 patients were produced by a propensity-matched analysis in these 256 patients, to match with SP group as a MP group. There were 26 males and 42 females at age of 54-62 (59.3±10.3) years in the SP group. There were 32 males and 36 females at age of 50-66 (61.5±9.4) years in the MP group. Perioperative outcomes were compared between the two groups. ResultsAll operations were accomplished successfully, without conversion to thoracotomy. Most postoperative outcomes were similar in intraoperative blood loss (136.3±22.7 ml vs. 142.2±20.3 ml), conversion (4.4% vs. 7.4%), lymph node dissection number (19.9±3.5 vs. 20.0±3.0), station (7.9±2.3 vs. 8.3±2.1), postoperative drainage volume (761.4±182.3 ml vs. 736.9±176.4 ml), chest drainage duration (5.2±1.5 d vs. 5.8±1.8 d), length of hospital stay (5.5±2.0 d vs. 5.0±2.5 d), and postoperative complications (2.9% vs. 7.4%) between the two groups (P > 0.05). There were statistical differences in operation time (138.2±20.3 min vs. 126.4±22.4 min), downtrend of pain scores (P=0.03), and patients' satisfaction level (8.8±1.4 vs. 7.3±2.3, P < 0.05). Concision Single-port thoracoscopic lobectomy is not inferior to multi-port and is a safe and feasible surgical procedure for the management of PNSCLC.