Objective    To investigate the clinical characteristics of uniportal and three-port subxiphoid video-assisted thoracoscopic surgery (XVATS) extended thymectomy. Methods    The clinical data of 60 consecutive patients of XVATS thymectomy in Xuzhou Central Hospital from January 2017 to May 2019 were retrospectively analyzed. There were 29 males and 31 females, with an average age of 53.1 (27.0-76.0) years. The patients were divided into an uniportal XVATS group (30 patients) and a three-port XVATS group (30 patients). The clinical effectiveness was compared between the two groups. Results    There was no significant difference in age, sex, body mass index, tumor size, intraoperative blood loss, postoperative time of thoracic tube indwelling and thoracic drainage, or postoperative hospitalization time between the two groups (P>0.05). There was no perioperative mortality, conversion to thoracotomy, thrombosis or mediastinal infection. The operation time of the uniportal XVATS group was significantly longer than that of the three-port group (87.5±19.0 min vs. 75.8±15.7 min, P=0.012). Besides, patients in the uniportal group had significantly lower pain score during 3-14 postoperative days than that of the three-port group (P=0.001). Conclusion    Uniportal XVATS extended thymectomy is feasible with less pain as compared with the patients using three-port XVATS, but it needs longer operation time at initial stage.