Cardiopulmonary complications account for up to 16% of endoscopic retrograde cholangiopancreatography (ERCP)–related adverse events. They have a reported incidence in large prospective studies ranging from 0.07%-2.4% but have been reported much more frequently in smaller single-center studies. This discrepancy in rates is probably because of lack of consensus definitions and inconsistent documentation owing to their often transient nature. Minor complications such as brief arrhythmias, transient desaturation, or fluctuation in blood pressure are frequent but may be of little clinical significance. Cardiopulmonary issues during ERCP may occur because of multiple mechanical and neuroendocrine mechanisms, which are potentiated by patient comorbidities and use of sedation. Deep sedation with propofol increases procedural success in therapeutic procedures and is not associated with increased risk of cardiorespiratory adverse effects when compared with other forms of sedation. Severe chronic obstructive pulmonary disease and a high American Society of Anesthesiologists Class (3 or more) have been associated with an increased risk of these complications and may require careful perioperative monitoring. From the standpoint of cardiopulmonary risk, ERCP may be performed in the supine or prone position in patients of most ages, with conscious sedation, monitored anesthesia care, or general anesthesia as appropriate for the case.