BACKGROUND/AIMS: Airway difficulties leading to cardiac arrest are frequently encountered during propofol sedation in patients undergoing gastrointestinal (GI) endoscopy. With a noticeable increase in the use of propofol for endoscopic sedation, we decided to examine the incidence and outcome of cardiac arrests in patients undergoing gastrointestinal (GI) endoscopy with sedation. PATIENTS AND METHODS: In this retrospective study, cardiac arrest data obtained from the clinical quality improvement and local registry over 5 years was analyzed. The information of patients who sustained cardiac arrest attributable to sedation was studied in detail. Analysis included comparison of cardiac arrests due to all causes until discharge (or death) versus the cardiac arrests and death occurring during the procedure and in the recovery area. RESULTS: The incidence of cardiac arrest and death (all causes, until discharge) was 6.07 and 4.28 per 10,000 in patients sedated with propofol, compared with non-propofol-based sedation (0.67 and 0.44). The incidence of cardiac arrest during and immediately after the procedure (recovery area) for all endoscopies was 3.92 per 10,000; of which, 72% were airway management related. About 90.0% of all peri-procedural cardiac arrests occurred in patients who received propofol. CONCLUSIONS: The incidence of cardiac arrest and death is about 10 times higher in patients receiving propofol-based sedation compared with those receiving midazolam-fentanyl sedation. More than two thirds of these events occur during EGD and ERCP.