ObjectiveTo compare the differences in clinical outcomes of artificial pneumothorax-assisted three-port, two-port, and uniportal thoracoscopic surgeries for the treatment of mediastinal tumors. Methods A retrospective analysis was conducted on clinical data of patients who underwent mediastinal tumor surgery in the Department of Thoracic Surgery at the General Hospital of Northern Theater Command from September 2020 to November 2024. Patients were divided into three groups based on the surgical approach: an artificial pneumothorax-assisted three-port thoracoscopy group, a two-port thoracoscopy group, and a uniportal thoracoscopy group. Perioperative data including operation time, intraoperative blood loss, postoperative hospital stay, chest tube indwelling rate, postoperative drainage volume, chest tube duration, and postoperative pain visual analogue scale (VAS) scores were compared among the three groups. Results A total of 308 patients were included. The artificial pneumothorax-assisted three-port thoracoscopy group comprised 75 patients [29 males, 46 females; median age: 57 (IQR: 47, 62) years]. The two-port thoracoscopy group included 127 patients [49 males, 78 females; median age: 52 (IQR: 43, 60) years], and the uniportal thoracoscopy group included 106 patients [48 males, 58 females; median age: 52.5 (IQR: 42, 62) years]. The operation time in the artificial pneumothorax-assisted three-port thoracoscopy group [74 (62, 99) min] was significantly shorter than that in the two-port thoracoscopy group [91 (71, 118) min] and the uniportal thoracoscopy group [90 (68, 110) min] (P<0.05). Intraoperative blood loss [30 (20, 75) mL] was also significantly less than that in the two-port thoracoscopy group [55 (30, 105) mL] and the uniportal thoracoscopy group [55 (30, 100) mL] (P<0.05). Regarding postoperative recovery, the length of hospital stay in the artificial pneumothorax-assisted three-port thoracoscopy group [2 (2, 4) days] was shorter than that in the two-port thoracoscopy group [3 (2, 5) days] and the uniportal thoracoscopy group [3 (3, 6) days] (P<0.05). On postoperative day 1 (POD1), the VAS score in the artificial pneumothorax-assisted three-port thoracoscopy group [4 (3, 4) points] was lower than that in the two-port thoracoscopy group [4 (3, 5) points] and the uniportal thoracoscopy group [4 (3, 5) points] (P<0.05). The chest tube indwelling rate (52.0%) was significantly lower than that in the two-port thoracoscopy group (92.9%) and the uniportal thoracoscopy group (84.9%) (P<0.05). POD1 chest tube drainage volume [80 (0, 105) mL] and chest tube duration [1 (0, 2) days] were also significantly less or shorter than those in the two-port thoracoscopy group [110 (80, 150) mL, 2 (1, 2) days] and the uniportal thoracoscopy group [100 (50, 150) mL, 1 (1, 2) days], respectively (P<0.05). Conclusion All three different surgical approaches for mediastinal tumors are safe and effective. Artificial pneumothorax-assisted three-port thoracoscopic surgery demonstrates comprehensive advantages in terms of operation time, intraoperative blood loss, and postoperative recovery.