Background <p>Oxygen support is crucial during sedated gastrointestinal endoscopic procedures, as sedation may cause airway collapse, leading to hypoxemia. While nasal cannula (NC) is the most used oxygen delivery method, the procedural oxygen mask (POM) has emerged as an alternative. This study aims to compare the effects of POM and NC on respiratory complications and hemodynamic parameters in patients undergoing sedated endoscopy.</p> Methods <p>This prospective observational study included 350 adult patients undergoing elective endoscopy. Patients were divided into two groups based on patient preference: procedural oxygen mask (POM, n = 200) and nasal cannula (NC, n = 150). Oxygen support was administered using either POM or NC, and hemodynamic and respiratory parameters, including peripheral capillary oxygen saturation (SpO₂), blood pressure, and heart rate, were monitored throughout the procedure. Respiratory complications, such as hypoxemia (defined SpO₂ &lt; 93%), were also recorded for analysis.</p> Results <p>The POM group showed significantly higher SpO₂ values at 1, 5, 10, and 15&#xa0;min (p &lt; 0.001). Hypoxemia rates were lower in the POM group (2.5%) compared to the NC group (6.7%) (p = 0.028). The POM group also had significantly lower systolic and diastolic blood pressures and a more stable mean arterial pressure (p &lt; 0.001). Recovery time was longer in the POM group (p &lt; 0.001), likely due to deeper sedation levels.</p> Conclusion <p>POM provides superior oxygen support and hemodynamic stability compared to NC, making it a safer option for sedated gastrointestinal endoscopic procedures. Despite older age and higher ASA scores in the POM group, it showed better respiratory outcomes and lower blood pressure fluctuations, demonstrating efficacy in higher-risk patients.</p> Clinical Trials <p><a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a>; Registration Number: NCT05684900; Registration Date: 29.11.2022.</p>