The study investigated whether oxygen reserve index (ORI) monitoring could reduce the incidence of low oxygen saturation during deep sedation for hysteroscopy. A randomized controlled trial enrolled 400 patients divided into four groups according to whether ORI monitoring was used and how oxygen was administered (facial or nasal). The results showed that ORI monitoring significantly reduced the incidence of low oxygen saturation to 18–21.4% compared to 51.5% in the groups without ORI monitoring. Patients with ORI monitoring required a shorter duration of assisted ventilation and achieved higher values of oxygen saturation during the procedure. The absolute risk reduction between the groups with and without ORI monitoring was 41%, meaning that only 3 patients needed to be monitored to prevent one case of low saturation. Nasal oxygen administration caused mild to moderate sore throat compared to facial administration.