Ongoing improvements in technique and instruments for video-assisted thoracoscopic surgery (VATS) have made minimally-invasive uniportal VATS lobectomy a reality. However, the outcomes of the procedure are still under investigation, and at present, uniportal VATS lobectomy is performed infrequently at most hospitals. We have therefore reviewed our outcomes with this procedure in an attempt to validate its safety, efficacy, and feasibility. We retrospectively analyzed and compared perioperative data for patients who underwent uniportal, two-port, and traditional three-port VATS lobectomy between January 2015 and December 2015 at our hospital. Among 257 patients who had successful VATS lobectomy during the study period, 73 underwent uniportal VATS, 86 underwent two-port VATS, and 98 underwent traditional three-port VATS. There were no surgical or 30-day postoperative mortalities, and no significant differences in operative times, blood loss, number of lymph nodes retrieved and nodal stations explored, drainage times, length of hospital stay, or postoperative complications among the three groups. The visual analogue scale (VAS) pain scores were significantly lower in the uniportal VATS group after surgery (P < 0.05). Uniportal VATS lobectomy is a safe and feasible surgical procedure that is associated with decreased surgical trauma and less postoperative pain compared to traditional VATS. Further long term follow-up analyses in large numbers of patients are ongoing.