Background: In recent years, opportunities to conduct anatomical segmentectomies for early stage lung cancer, metastatic lung tumor, and so on have been increasing. Generally, uniportal video-assisted thoracoscopic surgery (U-VATS) uncommon segmentectomy is technically more complicated because of limited angulation compared to multiportal VATS (M-VATS) and the need to treat peripheral vessels/ bronchi compared to common segmentectomy. This study aimed to determine the safety and feasibility of U-VATS uncommon segmentectomy compared with U-VATS common segmentectomy and M-VATS uncommon segmentectomy. Methods: We retrospectively reviewed the medical records of 76 patients in the M-VATS group and 45 patients in the U-VATS group who underwent VATS segmentectomy from January 2015 to December 2020. During that period, the perioperative results of U-VATS uncommon (n=22) segmentectomy were compared with those of U-VATS common (n=23) and M-VATS uncommon (n=37) segmentectomy. Uncommon segmentectomy was defined as any segmentectomy other than segmentectomies of the lingual, basilar, or superior segment of the lower lobe (S6), and upper division of the left upper lobe. All patients in our department underwent preoperative three-dimensional computed tomography (3D-CT) angiography and bronchography to image bronchovascular structures and determine the resection line. Results: Patients characteristics were similar between the U-VATS uncommon segmentectomy group and the U-VATS common segmentectomy group or the M-VATS uncommon segmentectomy group. In U-VATS, there were no significant differences between common and uncommon segmentectomy in operation time, postoperative drainage, postoperative hospitalization, and postoperative complications. Comparing M-VATS and U-VATS uncommon segmentectomies, operation time (145±35 vs. 185±44 min, P<0.001) and postoperative hospitalization (3.1±1.6 vs. 4.2±1.8 days, P=0.02) were significantly shorter in the U-VATS group than in the M-VATS group. There were no significant differences in blood loss, intraoperative bleeding, duration of postoperative drainage and postoperative complications. Conclusions: In U-VATS, both types of segmentectomies can be achieved with similar results. Moreover, U-VATS shortened operation time and postoperative hospitalization in uncommon segmentectomy compared with conventional M-VATS. U-VATS is a useful approach for uncommon segmentectomy.