Objective <p>There were two different airway management methods: inserting a 5.0-sized reinforced endotracheal tube through the nose to the front of the glottis, and using an oxygen mask combined with a nasal oxygen tube for oxygen delivery. This study aimed to evaluate the safety and efficacy of these two methods for painless fiberoptic bronchoscopy (FB) performed under deep sedation anesthesia with preserved spontaneous breathing.</p> Methods <p>A total of 64 patients undergoing elective painless FB were randomly assigned to either the 5.0-sized reinforced endotracheal tube group (Group E) or the oxygen mask combined with a nasal oxygen tube group (Group C). In group E, patients were received a 5.0-sized reinforced endotracheal tube which was inserted through the nostrils to the front of the glottis and connected to the anesthesia machine respiratory circuit for ventilation. In group C, patients were administered an oxygen mask in combination with a nasal oxygen tube, both connected to the anesthesia machine respiratory circuit. The primary outcome was the incidence of transient hypoxia during the procedure. The secondary outcomes covered the hemodynamics, time metrics, coughing scores, satisfaction scores, drugs consumption, numbers of remedies, willing to repeat FB and the incidence of adverse events.</p> Results <p>The incidence of transient hypoxia was significantly lower in group E (<i>P</i> &lt; 0.05). Compared with group C, patients in group E had significantly shorter induction times, lower coughing scores at immediately after the bronchoscope passed the glottis (T2), lower midazolam consumption and numbers of remedies though consumption of remifentanil, propofol, and dexmedetomidine was higher (<i>P</i> &lt; 0.05). Additionally, Patients in group E exhibited lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) values from T2 to end of FB (T5), as well as lower heart rate (HR) at T2, while the oxygen saturation (SpO₂) was significantly higher at T2 (<i>P</i> &lt; 0.05). Furthermore, there were no significant differences in the incidence of adverse events between the two groups (<i>P</i> &gt; 0.05).</p> Conclusions <p>Our findings suggest inserting a 5.0-sized reinforced endotracheal tube for airway management is superior to receiving the oxygen mask combined with a nasal oxygen tube undergoing FB. This method provides lower incidence of transient hypoxia and better hemodynamic stability, which makes it to be a more safe and effective choice in clinical practice.</p> Trial registration <p>This study was registered on chictr.org.cn (20/02/2023, ChiCTR2300068448).</p>