Prone positioning of patients is a routine occurrence in procedural suites and operating rooms (ORs). However, the physiological changes that occur with prone positioning are frequently underappreciated by proceduralists, surgeons, and anesthesiologists. This may be related to a sense of the routine or a lack of familiarity with physiological changes that accompany the prone position. The prone position, while aiding visualization and cannulation of the ampulla of Vater during endoscopic retrograde cholangiopancreatography (ERCP), can induce physiological changes such as reduced preload, inferior vena cava filling, and cardiac output; it can also increase intrathoracic pressure and mediastinal compression. Anesthetic agents can further impact cardiopulmonary physiology, decreasing systemic vascular resistance and reducing cardiac contractility. In addition, the transition from negative to positive pressure ventilation following endotracheal intubation can increase pulmonary artery pressures and right ventricular (RV) strain. Therefore, caution is needed with patients who have RV dysfunction, pulmonary hypertension, or preload dependency, as they may not tolerate prone positioning. We describe a case in which a 73-year-old male patient scheduled for an ERCP suffered cardiac arrest after being transitioned to the prone position. The patient was repositioned in the supine position and resuscitated. The case was completed in the supine position.