BACKGROUND Substernal thyrotoxic multinodular goiter (MNG) shows signs and symptoms as a result of compression of adjacent organs and thyrotoxicosis. However, acute airway obstruction is rarely caused by substernal thyrotoxic MNG. METHODS We have described a 56-year-old Japanese woman who demonstrated acute airway obstruction because of compression of the airway by substernal thyrotoxic MNG. She had been diagnosed with substernal thyrotoxic MNG 6 years back. However, because she was unwilling to undergo surgery to remove substernal thyrotoxic MNG, she was treated with methimazole. The patient maintained normal thyroid function with this therapy for 6 years. However, after 6 years the patient was admitted to our hospital because of severe dyspnea. Physical examination revealed inspiratory stridor, which indicated an airway obstruction caused by substernal thyrotoxic MNG. Airway intubation and subtotal thyroidectomy were performed. After the surgery, the dyspnea ameliorated. The general condition of the patient remained good 6 months after the surgery. CONCLUSIONS This case clearly demonstrates the need for careful monitoring of substernal thyrotoxic MNG, because it may lead to an airway obstruction.