Giant left atria are defined as those measuring larger than 8 cm and are typically found in patients who have rheumatic mitral valve disease with severe regurgitation. Enlargement of the left atrium may create compression of the surrounding structures such as the esophagus, pulmonary veins, respiratory tract, lung, inferior vena cava, recurrent laryngeal nerve, and thoracic vertebrae and lead to dysphagia, respiratory dysfunction, peripheral edema, hoarse voice, or back pain. However, a huge left atrium is usually associated with rheumatic mitral valve disease but is very rare in a normally functioning prosthetic mitral valve, as was the case in our patient. A 46-year-old woman with a past medical history of mitral valve replacement and chronic atrial fibrillation was admitted to our hospital with a chief complaint of cough and shortness of breath, worsened in the last month. Physical examination showed elevated jugular venous pressure, respiratory distress, cardiac cachexia, heart failure, hepatomegaly, and severe edema in the legs. Chest radiography revealed an inconceivably huge cardiac sell-out. Transthoracic echocardiography demonstrated a huge left atrium, associated with thrombosis, and normal function of the prosthetic mitral valve. Cardiac surgery with left atrial exploration for the extraction of the huge thrombosis and De Vega annuloplasty for tricuspid regurgitation were carried out. The postoperative course was eventful due to right ventricular failure and low cardiac output syndrome; and after two days, the patient expired with multiple organ failure. Thorough literature review showed that our case was the largest left atrium (20 × 22 cm) reported thus far in adults with a normal prosthetic mitral valve function.