Objective. The purposes of this study were to evaluate the feasibility, safety, and advantages of nonintubated video-assisted thoracoscopic surgery (VATS) under epidural anesthesia, by comparing with the performance of conventional approaches. Patients and methods. A total of 354 patients (245 men and 109 women) were recruited in this study. The surgical procedures included bullae resection, pulmonary wedge resection, and lobectomy. The anesthetic technique (epidural vs general) was selected randomly. Patients who underwent nonintubated VATS under epidural anesthesia comprised the intervention group, and patients who received VATS under general anesthesia with double lumen tube comprised the control group. Results. In total, 167 patients were included in the intervention group, and 180 patients were included in the control group. The 2 treatment groups of bullae resection showed significant differences in postoperative fasting time, duration of postoperative antibiotic use depending on the time when the white blood cells decreased to normal levels, and duration of postoperative hospital stay (P < .05). Nonintubated VATS is associated with a decreased level of inflammatory cytokines (P < .05). Conclusion. VATS under anesthesia with nontracheal intubation is safe and feasible, and has demonstrated advantages, including shorter postoperative fasting time, shorter duration of antibiotic use, and shorter hospital stay, compared with VATS under general anesthesia with double lumen tube.