Background <p>Hypoxemia is the most common adverse reaction during sedated hysteroscopy. Obesity is a risk factor for hypoxemia. For hysteroscopy, propofol is the most commonly used sedative. However, it can cause dose-dependent respiratory depression. This drawback has driven the search for sedatives with less respiratory depressant effects. Remimazolam is a new benzodiazepine drug with several advantages, including minimal impact on the respiratory and circulatory systems. This study aims to compare remimazolam and propofol in terms of safety and efficacy in patients with overweight or obesity who are undergoing sedated hysteroscopy.</p> Methods <p>This prospective, single-center, randomized, single-blind, controlled clinical trial will be conducted to examine the effect of remimazolam on the incidence of severe hypoxemia in patients with overweight or obesity. Patients (<i>n</i> = 600) scheduled to undergo sedated hysteroscopy will be randomly assigned to either the control or experimental group and will be sedated using propofol or remimazolam, respectively.</p> Discussion <p>The main objective of this study is to determine whether remimazolam can reduce the incidence of severe hypoxemia in patients with overweight or obesity during hysteroscopy. The results of this study are expected to provide evidence on the safety and efficacy of remimazolam in patients with overweight or obesity, which will enhance patient comfort and safety during sedated hysteroscopy.</p> Trial registration <p>ClinicalTrials.gov NCT06187896. Registered on January 3, 2024.</p>