Abstract: Objective To evaluate the therapeutic efficacy and safety of iodine-131 therapy for large goiter complicated by hyperthyroidism. Methods After the diagnosis of large goiter complicated by hyperthyroidism was established, the weight of the patient’s thyroid gland was determined, and the doses of iodine-131 calculated according to the formula currently available. After a single dose of oral iodine-131 capsule, the patients were observed for the therapeutic efficacy and side effects. Some patients were given the second or even the third dose of iodine-131. Results All of the 38 patients were cured by 1 to 3 single doses of iodine-131 therapy, of whom 23 (60.5%) needed only a single dose for the cure, 13 (34.2%) required the second dose, and 2 (5.3%) necessitate a third dose. Hypothyroidism occurred in 4 cases (10.5%), and none of the patients developed hyperthyroidism crisis and dyspnea. Conclusions Iodine-131 therapy for serious goiter with hyperthyroidism is safe and effective, which can be used as a routine therapy for this condition.