Myxedema coma is a life-threatening endocrine emergency with a high mortality rate resulting from severe insufficiency of thyroid hormones. Intravenous levothyroxine replacement is considered the standard therapy for myxedema coma in many countries. In Japan, however, although there are diagnostic criteria highly suggestive or diagnostic for myxedema coma, no management strategy has been established, despite the availability of levothyroxine. Here we report a 75year-old man with a history of Alzheimer's disease and schizophrenia who developed somnolence and generalized edema. Except for a pulse rate of 60 bpm, his vital signs and blood oxygen level were stable. Thyroid studies showed an elevated serum thyrotropin level of 219.2 μU/mL and a decreased serum free-thyroxine level of 0.15 ng/dL. On this basis he was diagnosed as having hypothyroidism rather than being highly suggestive for myxedema coma. Daily oral levothyroxine 25 μg was initiated and increased to 50 μg 3 days later. Seven days after being started on levothyroxine, the patient suddenly developed impaired consciousness, hypoxemia, hypotension, hypothermia, and hyponatremia. Electrocardiography revealed junctional bradycardia with Osborne J-wave. Myxedema coma was therefore diagnosed. He went into cardiac arrest in the emergency room but was resuscitated. Despite subsequent intravenous administration of hydrocortisone and levothyroxine, as well as intensive supportive care, he eventually died 12 hours after hospital admission. This case illustrates some of the challenges associated with the management of patients with signs highly suggestive/diagnostic of myxedema coma, including the optimal loading dosage and intervention timing of thyroid hormone replacement.