We describe the case of severe diffuse multivalvular disease associated with fenfluramine-phentermine (Fen-Phen) in a 52-year-old patient who presented to the echocardiography laboratory for evaluation of a new heart murmur and ultimately required isolated aortic valve replacement. The patient was known to have a transthoracic echocardiogram 1 year before starting the diet pill combination that showed no significant valvular disease. Pathological evaluation of the excised aortic valve was consistent with that described with Fen-Phen use. Transesophageal echocardiography played an important role in defining unique features associated with the valvular disease and in intraoperative management of the patient.