Hypoxemia is a common complication in older patients during postoperative recovery and can cause pulmonary complications. Therefore, reducing the incidence of postoperative hypoxemia is a clinical concern.To investigate the clinical efficacy of high-flow nasal cannula oxygen (HFNCO) in the resuscitation period of older orthopedic patients.In this prospective randomized controlled trial, 60 older patients who underwent orthopedic surgery under general anesthesia were randomly divided into two groups: those who used conventional face mask and those who used HFNCO. All patients were treated with 60% oxygen for 1 h after extubation. Patients in the conventional face mask group were treated with a combination of air (2 L) and oxygen (2 L) using a traditional mask, whereas those in the HFNCO group were treated with HFNCO at a constant temperature of 34 °C and flow rate of 40 L/min. We assessed the effectiveness of oxygen therapy by monitoring the patients' arterial blood gas, peripheral oxygen saturation, and postoperative complications.The characteristics of the patients were comparable between the groups. One hour after extubation, patients in HFNCO group had a significantly higher arterial partial pressure of oxygen (paO2) than that of patients in conventional face mask group (P < 0.001). At extubation and 1 h after extubation, patients in both groups showed a significantly higher arterial partial pressure of carbon dioxide (paCO2) than the baseline levels (P < 0.001). There were no differences in the saturation of peripheral oxygen, paO2, and paCO2 between the groups before anesthesia and before extubation (P > 0.05). There were statistically significant differences in paO2 between the two groups before anesthesia and 1 h after extubation and immediately after extubation and 1 h after extubation (P < 0.001). However, there were no significant differences in the oxygen tolerance score before leaving the room, airway humidification, and pulmonary complications 3 d after surgery between the two groups (P > 0.05).HFNCO can improve oxygen partial pressure and respiratory function in elderly patients undergoing orthopedic surgery under general endotracheal anesthesia. Thus, HFNCO can be used to prevent postoperative hypoxemia.©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.