Abstract: Objective To analyze the clinical effective of two medication methods in the ¹³¹I treatment of severe goiter patients associated with hyperthyroidism. Methods The patients were divided two groups: SDM group (Secondary drug medication）, after taking moderate doses of ¹³¹I (3.145～3.33 MBq / per gram of thyroid tissue) and applying thyroid weight loss treatment for 3 to 6 months, for the patients not healed a secondary treatment by giving them therapeutic doses of ¹³¹I according to the specification standard of per gram of thyroid tissue; ODM group (Once drug medication), for these treated patients an once ¹³¹I treatment according to the therapeutic ¹³¹I dose （4.25～4.65MBq/ per gram of thyroid tissue）. The comprehensive efficacy, including cure rate, early hypothyroidism and safety in SDM and ODM group were analyzed. Results There was no significant difference in the two groups of SGAH patient’s gender, age, thyroid weight, disease course and their overall cure rate after secondary treatment (P> 0.05). There were significant differences in the cure rate between the SDM weight loss treatment and the ODM treatment, the two group’s secondary medication cure rate and early hypothyroidism rate. Among various thyroid weight groups with SDM, the differences of their weight loss treatment cure rate and secondary cure rate were significant. Also, among various thyroid weight groups with ODM, the differences of their once treatment cure rate and secondary cure rate were significant (P＜0.05）. Conclusion SDM is significantly superior to ODM，in the treatment security as well as early hypothyroidism rate. ODM is better than SDM in cure time and cost of treatment.