Background <p>Postoperative pulmonary complications (PPCs) are severe and are of particular concern in older adult patients undergoing laparoscopic gastrointestinal surgery. Both 40% and 80% fraction of inspired oxygen (FiO₂) are commonly used for anesthesia. Presently, whether 40% FiO₂ can increase the oxygenation index of patients 48&#xa0;h postoperatively and reduce PPCs remains controversial. Moreover, no clear consensus exists for older adult patients. Therefore, this study aims to compare the effects of low FiO₂ (40%) and high FiO₂ (80%) levels on postoperative pulmonary function in older adult study participants undergoing laparoscopic gastrointestinal surgery.</p> Methods <p>This multicenter, prospective, parallel-cohort, randomized controlled clinical trial will include 1098 older adult participants aged ≥ 65 years old undergoing laparoscopic gastrointestinal surgery, from 16 clinical trial sites across China. Participants will be randomized, as per a 1:1 ratio to two cohorts, the “L” and “H” cohorts, to receive low FiO₂ (40%) and high FiO₂ (80%) levels, respectively. The primary outcome measure is the 48-h postoperative oxygenation index between the two cohorts. The secondary outcome measures include the other blood gas analysis results, PPCs within 7&#xa0;days, and 30-day mortality rate.</p> Discussion <p>This study of elderly patients undergoing laparoscopic gastrointestinal surgery with different intraoperative oxygen concentrations at high risk for pulmonary complications. All subjects were followed up for up to 30&#xa0;days for pulmonary function, postoperative complications, etc. Randomization was performed separately at 16 sites.</p> Trial registration <p>ClinicalTrials.gov NCT06359106. Registered and posted on April 11, 2024.</p>