Endoscopic ultrasonography-guided transesophageal pericardiocentesis was performed for a posteriorly located effusion not amenable to transthoracic drainage in a 58-year-old woman with a history of recurrent breast adenocarcinoma who presented with dyspnea. The patient had a pericardial effusion that resulted in cardiac tamponade. Transthoracic pericardiocentesis was unsuitable because of the posterior location of the effusion. Pericardiocentesis via the transesophageal route was performed. The pericardial sac was punctured with a 19-gauge needle, and 245 mL of pericardial fluid were aspirated, resulting in the resolution of the tamponade physiology. Endoscopic ultrasonography-guided transesophageal drainage is a novel and promising therapeutic option for posteriorly located pericardial effusions.