Objective To investigate the application effect of single hole thoracoscopic resection in patients with spontaneous pneumothorax and pulmonary bullae, and further analyze its clinical safety. Methods The clinical data of 80 patients with spontaneous pneumothorax and pulmonary bullae admitted to Central Hospital of Zhuanghe City from January 2018 to January 2021 were retrospectively analyzed. They were divided into single hole group and three hole group according to envelope method, with 40 cases in each group. The single hole group was treated with single hole thoracoscopic resection, and the three hole group was treated with three hole thoracoscopic resection. The amount of intraoperative bleeding, operation time, hospital stay, incidence of complications, serum white blood cell (WBC) and Creactive protein (CRP) were compared between the two groups. Results The intraoperative blood loss of the single hole group was less than that of the three hole group, and the operation time and hospital stay of the single hole group were shorter than those of the three hole group, the differences were statistically significant (P＜0.05). The postoperative complication rate and the 1 year recurrence rate in the single hole group were lower than those in the triple hole group, the differences were statistically significant (P＜0.05). Postoperative serum WBC and CRP levels were higher than preoperative levels in both groups, and postoperative serum WBC and CRP in the one hole group were lower than those in the three hole group, the differences were statistically significant (P＜0.05). Conclusion Thoracoscopy resection has a significant effect on spontaneous pneumothorax complicated with pulmonary bullae. The efficacy, recovery efficiency and safety of single hole thoracoscopic resection are better than three hole thoracoscopic resection, which is worthy of further popularization.