The study aimed to assess the response of Graves Disease (GD) and Toxic MultiNodular Goiter (TMNG) to RAI-131 therapy within a follow up duration of 6 months - 3 years. Methods: 200 patients with thyrotoxicosis were evaluated at Nuclear Medicine Unit ,Cairo University during the period of January 2007 till March 2012.All patients (120 females and 80 males) were subjected to full history taking, clinical examination ,lab tests (FT3, FT4,TSH and thyroid antibodies), neck ultrasound, thyroid scan with Tc-99m pertechnetate. Thyroid gland uptake was estimated for all cases. Different doses RAI-131 therapy (12 – 29 mCi) were given to all patients with 3 years follow up guided by T3,T4 and TSH Results. The current study population included 100 patients of GD (group1) and 100 patients of TMNG (group2), Mean age in group1 was 33±9.8 while mean age in group 2 was 42±11.78 , with significant difference between age and prevalence of each type of thyrotoxicosis (P< 0.001). In group 1, 40 patients received 12 mCi of RAI-131, while 35 patients received 15 mCi. Both of them showed clinico-laboratory evidence of euothyroid state, where as the rest of this group (25 patients) received 20 mCi after which most of them developed hypothyroidism. On the other hand, group 2, it was divided into 35 patients received 20 mCi, 45 patients received 25 mCi & the remaining 20 patients received 29 mCi. The former two sub groups showed predominance of euothyroid state on follow up, while those received 29 mCi, 8 of them developed hypothyroidism. As regard number of doses, only 16 out of the 200 patients received repeated doses of RAI-131, while the rest received single dose of RAI-131. There was significant high incidence of hypothyroidism among patients received large doses of I-131 ranging 25 - 29 mCi compared to those received small doses ranging from 12 to 15 mCi, with P-value (0.05). Conclusion: RAI-131 has a very important role in treating both GD and TMNG. Different doses of RAI-131 has different impact on the thyroid gland function. Hypothyroidism is a common outcome after high dose of RAI-131 treatment.