Amiodarone-induced thyrotoxicosis (AIT) is a potentially life-threatening complication of amiodarone therapy, particularly challenging in patients with significant cardiovascular disease. The case is presented of a 77-year-old man with advanced cardiac comorbidities who developed severe thyrotoxicosis during amiodarone treatment. AIT type II was diagnosed based on clinical features, laboratory results, and Doppler ultrasonography. Despite intensive therapy with glucocorticoids, beta-blockers, antithyroid drugs, lithium carbonate, and sodium perchlorate, no improvement was achieved. Therapeutic plasma exchange (TPE) was introduced as a rescue strategy. 4 sessions resulted in significant hormonal reduction and clinical stabilization, enabling safe total thyroidectomy without perioperative complications. This case highlights the limitations of conventional therapy in severe AIT and supports early consideration of TPE in selected high-risk patients requiring rapid stabilization before definitive treatment.