INTRODUCTION: During sedation for gastroscopy, hypoxaemia represents the most common adverse event. The objective of this trial is to assess the efficacy and safety of bilevel positive airway pressure (BPAP) for the prevention of hypoxaemia, in comparison with nasal cannula oxygen therapy, among patients predisposed to hypoxaemia during sedation for gastroscopy. METHODS AND ANALYSIS: This randomised controlled trial (RCT) will include 616 patients at risk of hypoxaemia when undergoing gastroscopy, including those with advanced age, frailty, American Society of Anesthesiologists grades III-IV, obesity, obstructive sleep apnoea-hypopnoea syndrome, cardiac disease, respiratory disease and diabetes. The patients will be randomly assigned to either the BPAP or nasal cannula group in a 1:1 ratio. The primary analysis for this study will use the modified intention-to-treat analysis set. The primary outcome is defined as the incidence of hypoxaemia (SpO ETHICS AND DISSEMINATION: The Ethics Committee of the First Affiliated Hospital of Zhengzhou University reviewed and approved this RCT (Scientific Research Ethics Review: 2023-KY-0815-003). Subsequently, the outcome will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2400084596.