<p>Patients with obstructive sleep apnea or obesity are at high risk for hypoxemia during sedated gastroenteroscopy. This meta-analysis compares the efficacy of bilevel or continuous positive airway pressure versus conventional oxygen therapy in preventing hypoxemia and reducing airway interventions. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs up to September 2025. Eight RCTs (1012 patients) were included; all controls received conventional oxygen therapy. Compared to conventional oxygen therapy, bilevel or continuous positive airway pressure was associated with a significant reduction in hypoxemia (OR 0.26, 95% CI 0.16–0.42), severe hypoxemia (OR 0.15, 95% CI 0.05–0.39), and need for jaw lift (OR 0.21, 95% CI 0.14–0.32), with no significant difference in nausea/vomiting. Subgroup analyses consistently favored bilevel or continuous positive airway pressure. The simplified device SuperNO₂VA also significantly reduced hypoxemia and jaw lift. This meta-analysis suggests that bilevel or continuous positive airway pressure is associated with reduced hypoxemia and airway interventions versus conventional oxygen therapy in high-risk patients undergoing sedated gastroenteroscopy. However, these findings are based on physiological surrogate outcomes, and patient-centered clinical endpoints remain unreported. Limitations include the lack of a blinded design and comparison with high-flow nasal cannula therapy. Future RCTs should compare bilevel or continuous positive airway pressure with high-flow nasal cannula and incorporate patient-centered outcomes to confirm clinical benefit. PROSPERO CRD420251129870.</p>