Objective To observe the effects of nasal humidification and high flow ventilation intervention on vital signs and incidence of hypoxemia in elderly overweight patients undergoing initial gastroscopy. Methods 98 elderly overweight patients who underwent the first gastroscopy in Zhenzhou Hospital of Traditional Chinese Medicine from December 2021 to December 2023 were selected as research samples and divided into 2 groups by drawing lots. Before the examination, 49 patients in the control group received conventional nasal catheter oxygen inhalation, and the other 49 patients in the observation group were given nasal humidification and high flow ventilation, all of which were interventionized until the examination was completed. The vital signs and recovery time, time of examination, incidence of hypoxemia and adverse reactions during the examination were compared between the two groups. Results There was no significant difference in heart rate and mean arterial pressure between the two groups before anesthesia, after gastroscopy insertion and after recovery (P > 0.05). The success rate of one gastroscopy in the observation group was higher than that in the control group, and the time of examination and departure from hospital was shorter than that in the control group (P < 0.05). There was no significant difference in recovery time between the two groups (P > 0.05). The minimum Saturation of blood oxygen (SpO2) of the observation group was higher than that of the control group, the incidence of hypoxemia were lower than that of the control group (P < 0.05), and there was no statistical difference in the incidence of total adverse reactions between the two groups (P > 0.05). Conclusion In elderly overweight patients undergoing gastroscopy for the first time, nasal humidification and high flow ventilation can effectively maintain the stability of vital signs during the endoscopic examination, shorten the time of endoscopic examination and discharge from hospital, improve the success rate of one examination, reduce the occurrence of hypoxemia and is safer.