Background <p>To investigate the preventive effects of personalized positioning management on hypoxemia during sedated endoscopic examination in elderly patients with esophageal cancer (EC).</p> Methods <p>A retrospective observational study was conducted. We retrospectively reviewed the medical records of elderly patients with esophageal cancer who underwent sedated gastroscopy between January 2023 and June 2024. Patients who received personalized positioning management were assigned to the intervention group (<i>n</i> = 67), while those who underwent conventional left lateral decubitus positioning were assigned to the control group (<i>n</i> = 67). The incidence of hypoxemia, lowest peripheral oxygen saturation (SpO₂), severe hypoxemic events, examination time, sedative dosage, comfort scores, and incidence of adverse events were compared between the two groups. Binary logistic regression analysis was performed to identify factors associated with hypoxemia.</p> Results <p>In the intervention group, the incidence of hypoxemia was significantly lower; the lowest SpO₂ was distinctly higher; and the incidences of severe hypoxemia and hypoxemic events requiring intervention were lower. Personalized positioning management was identified as an independent protective factor against hypoxemia. A higher American Society of Anesthesiologists physical status classification (Class III) was an independent risk factor for hypoxemia. The intervention group had a shorter examination time, lower propofol dosage, higher comfort scores, and a lower incidence of adverse events.</p> Conclusion <p>Personalized positioning management effectively reduces both the incidence and severity of hypoxemia during sedated endoscopic examination in elderly patients with EC. This strategy demonstrates high clinical safety and feasibility.</p>