The prone position during anesthesia sometimes causes hemodynamic changes such as a decrease in blood pressure. These changes are caused by a decrease in venous return from venous pooling in the legs, and decreased left ventricular compliance secondary to increased intrathoracic pressure, when patients are placed prone with an Andrews frame. We report on a patient who experienced cardiac arrest in the prone position with the Andrews frame during lumbar laminectomy and posterior lumbar interbody fusion. After 1.25 h in the prone position, bradycardia and hypotension occurred. Ephedrine, atropine and epinephrine were infused intravenously, but bradycardia and hypotension progressed to asystole. Cardioinhibitory reflex was likely triggered by decreased venous return and increased intrathoracic pressure, and the patient developed cardiac arrest as a result.