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Objectives This study aimed to investigate the knowledge, attitude and practices (KAP) of patients undergoing gastrointestinal endoscopy regarding out-of-operating-room anaesthesia and sedation.Design A cross-sectional study.Setting The study took place at the Second Affiliated Hospital of Hainan Medical University in Haikou from January to June 2024.Participants A total of 638 participants were included, with 339 (53.13%) being male. Among them, 232 (36.36%) had previously received out-of-operating-room anaesthesia during gastrointestinal endoscopy.Interventions Participants completed a questionnaire designed to evaluate their KAP related to anaesthesia and sedation.Primary and secondary outcome measures The primary outcomes measured were knowledge scores (possible range: 0–10), attitude scores (possible range: 8–40) and practice scores (possible range: 6–30), which were derived from responses to the KAP questionnaire. Secondary outcomes included factors associated with proactive practices.Results Mean scores for KAP were 4 (1, 7), 31 (30, 35) and 24 (20, 27), respectively. Multivariate logistic regression analysis indicated that knowledge score (OR=1.210, p<0.001), attitude score (OR=1.273, p<0.001), female gender (OR=1.899, p=0.008) and agreeing to family presence (OR=1.772, p=0.014) were associated with proactive practices. Structural equation modelling showed knowledge directly influenced both attitude (β=0.761) and practices (β=0.733), while attitude directly influenced practices (β=0.791).Conclusions Patients displayed inadequate knowledge but positive attitudes and proactive practices regarding out-of-operating-room anaesthesia and sedation. Educational interventions by healthcare providers are recommended to improve patient knowledge, enhancing attitudes and practices.