BACKGROUND Nonintubated video-assisted thoracic surgery (NIVATS) has been demonstrated to be safe and effective in patients. However, the risk factors for intraoperative hypoxia are unclear. This retrospective study aimed to identify the risk factors for the development of intraoperative hypoxia in patients undergoing NIVATS. MATERIAL AND METHODS The study included patients who underwent NIVATS between January 2011 and December 2018. Intraoperative hypoxia was defined as SpO₂ ≤93%. Risk factors for hypoxia were identified by binary logistic regression analysis, and the characteristic distribution of patients with and without hypoxia was elaborated. RESULTS Of 2742 included patients, age, anesthesia method, the technical level of surgeons, stair-climbing ability, and type of thoracic procedure were associated with intraoperative hypoxia (P<0.05). The characteristics of patients with hypoxia were older age (P=0.011), higher body mass index and revised cardiac risk index level (P=0.033 and P=0.031), and lower composition of stair-climbing ≥22 m (P<0.001). These patients also had more anatomical lung surgery and mediastinal mass resection (P=0.033) and more epidural anesthesia (P=0.005). The surgeries were more likely to be performed by surgeons with less than 10 years of VATS training (P=0.009) and to have increased intraoperative maximum end-expiratory carbon dioxide partial pressure (P<0.001). These patients had a longer Intensive Care Unit stay (P<0.001), duration of chest-tube drainage (P=0.019), and postoperative hospitalization (P=0.003). CONCLUSIONS The current study suggests that old age and stair-climbing ability of patients, anesthesia method, thoracic procedures, and surgeon experience are risk factors for intraoperative hypoxia in patients undergoing NIVATS.