The C-Pulse System is an implantable, extra-aortic, non-blood-contacting counterpulsation device, investigational in the United States and intended for use as a heart assist device for heart failure (NYHA class III-ambulatory IV) patients. As long-term effects of this implantable extra-aortic counterpulsation device on the aortic wall structure are not well established, we examined the histological and clinical data of a patient supported on the device for 21 months. A 58-year-old woman diagnosed with nonischemic cardiomyopathy (NYHA III) remained symptomatic despite optimal medical therapy and dual chamber pacemaker. She was listed for heart transplant, and a C-Pulse device was implanted. One month after implantation, her symptoms improved from NYHA class III to class I, and her cardiac output increased from 3.5 to 5.5 L/min. She received a heart transplant 21 months after device implantation. Tissue samples from her ascending aorta were obtained. They appeared normal on macroscopic examination. Microscopic examination revealed a normal intima and media, with no disruption; a mild neutrophilic inflammation was noted on the adventitia. Extended extra-aortic counterpulsation with the C-Pulse device provided hemodynamics and symptoms improvement in a class III heart failure patient and does not appear to significantly alter aortic wall structures.