Endomyocardial biopsy remains the primary method for diagnosis of cardiac allograft rejection. Generally, endomyocardial biopsy is considered a relatively safe procedure in heart transplant recipients. Complications that have been reported are related to catheter insertion and include carotid arterial puncture, prolonged bleeding, vasovagal reaction, ventricular tachyarrhythmias, and transient conduction abnormalities. Serious complications such as right ventricular perforation with cardiac tamponade may also occur. Most complications are usually without significant long-term sequelae. This report describes an unusual case of atrioventricular fistula between the right atrium and left ventricle that occurred during a routine endomyocardial biopsy in a heart transplant recipient. Sudden hemodynamic compromise developed in this patient soon after heart biopsy associated with hemodynamic picture of high-output heart failure. Right heart catheterization, including oximetry, peripheral venous contrast echocardiography, color flow Doppler studies, and transesophageal echocardiography confirmed the diagnosis of fistulous communication between the right atrium and left ventricle, most likely through the membranous interventricular septum. Conservative medical management resulted in striking clinical improvement within 48 hours commensurate with spontaneous closure of the right atrium-to-left ventricle fistula documented by hemodynamic and echocardiographic studies.