Objectives Amiodarone-induced thyrotoxicosis (AIT) affects up to 3% of treated patients. Type 2 AIT (AIT2) is a destructive thyroiditis and is usually treated with medium-high oral doses of prednisone. As AIT may worsen the underlying heart disease, a rapid control of thyroid function is desirable. We aimed to determine whether a combined intravenous methylprednisolone (IVMP) pulses therapy associated to prednisone in the interpulse period can represent an efficient and safe alternative to urgent total thyroidectomy in patients with AIT2 not responsive to prednisone alone. Design and methods Patients presenting with a severe AIT2 studied in a tertiary referral Center from August 2018 to April 2019. We included four patients requiring a rapid improvement of thyroid function for their underlying cardiac disorders. The baseline doses of oral prednisone (range: 5–12.5 mg/day) and IVMP (range: 250–500 twice a week) were determined according to the severity of the thyrotoxicosis and were titrated based on clinical response. Results Combined treatment was effective in all patients in the prompt restoration of euthyroidism and no major adverse events were reported during the follow-up. In all cases, FT4 and FT3 levels normalized at 3–5 weeks of treatment. A permanent hypothyroidism was observed in one patient, 3 months after the discontinuation of treatment. Conclusions We report for the first time that the combined intravenous and oral steroid therapy is effective in patients with AIT2. The treatment is well tolerated and leads to a rapid improvement of thyroid function, avoiding urgent total thyroidectomy and favoring a quick functional recovery and rehabilitation of cardiac patients.