Objective To explore the safety and feasibility of spontaneous breathing anesthesia combined with tubeless uniportal thoracoscopy in pulmonary bullae surgery. Methods Totally 112 patients with pulmonary bullae in the Affiliated Hospital of Inner Mongolia Medical University from March 2015 to May 2017 were enrolled. According to the random number chosen by computer, the patients were randomly divided into two groups: a tubeless group (spontaneous breathing anesthesia combined with tubeless uniportalthoracoscopy) and a control group (uniportal thoracoscopy by general anesthesia with tracheal intubation) . There were 49 males and 7 females with an average age of 25.5±6.5 years in the tubeless group, and 50 males and 6 females with an average age of 23.5±4.5 years in the control group. The difference of the lowest intraoperative arterial oxygen saturation (SaO2), SaO2 at postoperative one hour, operation time, postoperative awakening time, hospital stay, hospitalization cost and postoperative pain score were analyzed. Results There was no significant difference between the two groups in the operation time, the lowest SaO2, SaO2 at one hour after the operation and the partial pressure of carbon dioxide (PaCO2). The awakening time and duration of postoperative hospital stay in the tubeless group was shorter than those in the control group (P=0.000). The cost of hospitalization in the tubeless group was less than that in the control group (P=0.000). The discomfort caused by urinary tract and visual analogue score (VAS) in the tubeless group were better than those in the control group. Conclusion It is safe and feasible to use spontaneous breathing anesthesia combined with tubeless uniportal thoracoscopy in pulmonary bullae resection.