Introduction During gastrointestinal endoscopy (GIE) procedures(upper/lower) performed under deep sedation, patients with coronary artery disease(CAD) have poorer tolerance, with higher incidence of hypotension and myocardial ischemia. Patients with CAD should particularly avoid hypoxemia caused by deep sedation and increased oxygen consumption caused by inadequate sedation. Recent data indicate that high-flow nasal oxygen therapy (HFNO) is recommended for preventing hypoxemia in high-risk patients. The data on cardiac cycle efficiency (CCE) from MostCare can be used to assess myocardial oxygen supply-demand balance in patients with CAD. HFNO may potentially improve myocardial oxygen supply during GIE under deep sedation. We hypothesize that compared to standard oxygen therapy (SOT), HFNO could improve CCE in patients with CAD. Methods and analysis The MEHIS (MostCare-Based Assessment of CCE in CAD Patients:HFNO versus SOT for GIE with sedation. The prospective single-center randomised controlled) study is a single-center randomized controlled trial comparing the effects of HFNO and SOT during GIE under deep sedation administered by anaesthesiologists in the procedure room in patients with CAD. Ninety patients will be randomly allocated in a 1:1 ratio to two parallel groups. The primary outcome is the difference in CCE levels between the two groups during sedation. Secondary outcomes are the incidence of hypotension(hypotension defined as a systolic blood pressure below 80 mmHg), values of BNP (brain natriuretic peptide), TnI (troponin I), and lactate levels at 6-12 hours post-operation,the occurrence of hypoxemia defined as SpO2 measurement equal to or below 92%, MostCare hemodynamic parameters excluding the primary outcome, interventions required to maintain upper airway patency, patient agitation episodes (assessed by touching the oxygen supply device), and presence of intraoperative adverse memories postoperatively. Keywords high-flow nasal oxygen therapy (HFNO); cardiac cycle efficiency (CCE); gastrointestinal endoscopy (GIE); coronary artery disease(CAD) Trial registration number ChiCTR2400086887 Strengths and limitations of this study 1. This is the first pragmatic randomized single-center study comparing HFNO to SOT for oxygenating patients with CAD undergoing GIE. 2. In contrast to comparing HFNO with high fraction of inspired oxygen (FiO2) typically used in SOT with low oxygen flow and consequently lower FiO2, this study adjusts gas flows to target roughly the same level of applied FiO2 in both groups. This approach aims to assess whether HFNO can improve CCE through positive end-expiratory pressure and/or dead space washout effects. 3. In SOT group, precise FiO2 cannot be guaranteed. That is why we utilized a pre-existing abacus to achieve the best equivalence. 4. Technically, blinding of practitioners and other nursing staff to the study groups is not feasible. However, the printout of recorded primary outcome measures is produced, allowing delayed reading by assessors blinded to treatment allocation. We employed a blind method in the study of patients. 5. In patients not undergoing endotracheal mechanical ventilation, MostCare data collection may exhibit slight bias due to respiratory influences. However, both groups in our study were conducted under sedation, and longitudinal comparisons were performed, thus minimizing the impact of such bias. 6. CAD patients with upper/lower gastrointestinal bleeding often suffer from anemia. We stratified CAD patients into anemic and non-anemic groups and compared the CCE under two oxygen delivery modes. This could provide a basis for further evaluating the oxygen therapy effectiveness of HFNO for anemic patients.