A 76-year-old female, with a history of asthma and tracheal bronchitis, presented with a non-ST elevation, myocardial infarction. Chest x-ray on admission showed a widened mediastinum, which was further evaluated with a computed tomography (CT) scan. It disclosed a giant substernal goiter compressing the trachea and the ascending aorta. Cardiac catheterization showed significant coronary disease unsuitable for percutaneous intervention; thus, the patient was scheduled for coronary artery bypass grafting. Single stage thyroidectomy immediately followed by coronary artery bypass was performed. After surgery, her upper airway symptoms were improved, and no cardiac events were noted. Collaboration between otolaryngology and thoracic surgery teams contributed to good outcomes for this patient with substernal goiter and severe cardiac disease.