Background: Single-port video-assisted thoracoscopic surgery (VATS) have been performed in Southeast Asian countries for several years. However, the outcomes of the single-port VATS are still under investigation. Objective: To compare the surgical outcomes between single-port VATS and multi-port VATS in pulmonary lobectomy and to validate its efficacy and safety. Materials and Methods: The outcomes of 130 patients that underwent VATS at the Central Chest Institute of Thailand between January 2015 and May 2018, were reviewed. Patients were classified into two groups, single-port, and multi-port VATS with 68 as single-port and 62 as multi-port cases. Patient characteristics and perioperative outcomes were analyzed and compared. Results: There were no significant differences in patient characteristics between the two groups. The single-port group had a lower Pain Numeric Rating Scale at 24 hours (p=0.022) and shorter length of hospital stay (p=0.044) than the multi-port group. The number of N2 lymph nodes retrieved in the single-port group was significantly higher than in the multi-port group (p=0.022) while other surgical outcomes were not significantly different. There were no significant differences in intraoperative and post-operative complications (p=0.338 and p=0.142, respectively) and no perioperative mortality in both groups. Conclusion: The authors’ experience showed that single-port VATS is a practical technique and safe procedure when compared to multi-port VATS. Keywords: Video-assisted thoracoscopic surgery (VATS), lobectomy, minimally invasive surgery