Objectives. The investigation was aimed to evaluate the safety and efficacy of glasses-free 3-dimensional (3D) video-assisted thoracoscopic surgery (VATS) versus 2D VATS for radical resection of non–small cell lung cancer (NSCLC). Methods. We reviewed the clinical data of patients with pathologically proven NSCLC who underwent glasses-free 3D (the 3D group) and 2D VATS radical lobectomy (the 2D group) with systematic lymph node dissection. The outcomes of this study included operative characteristics and safety of 2D and 3D VATS, and duration of lymphadenectomy of right stations 2 and 4. Results. A total of 190 patients were eligible for the study. The 2D group consisted of 108 patients while the 3D group included 82 patients. The 2 groups were comparable in demographic and baseline variables (P > .05). The median number of resected lymph nodes was 19 in both groups (P = .583). The median length of hospital stay was comparable between the 2 groups (2D, 7 days vs 3D, 8 days; P = .167). No operative mortality was reported in either group. Complications developed in 21 (19.4%) patients in the 2D group and 14 (17.1%) in the 3D group (P = .710). A subgroup analysis of patients who underwent right station 2 and 4 lymphadenectomy showed that the mean time for right station 2 and 4 lymph node dissection was significantly shorter in the 3D group than in the 2D group (3D, 430.9 ± 237.2 vs 2D, 648.6 ± 364.1 seconds; P < .001). Conclusions. Glasses-free 3D VATS and 2D VATS are comparable in operative characteristics and safety profile for radical resection of NSCLC. Glasses-free 3D visualization facilitates more rapid right-sided mediastinal lymphadenectomy.