The aim of this study was to evaluate response and compare the success rate of two different doses of iodine-131 ((131)I) therapy in the treatment of Graves' disease and investigate the factors that may affect outcome. A retrospective analysis was carried out on 321 patients treated with (131)I for Graves' disease. Group 1 (155 patients) received 8 mCi and group 2 (166 patients) received 12 mCi. The therapy was considered successful if euthyroidism or hypothyroidism was achieved within 1 year of therapy. The outcome was compared with multiple parameters. A significant difference in the outcome between the two groups was found in favor of the second group (P<0.001). Logistic regression analysis showed that lower dose, technetium-99m pertechnetate thyroid uptake greater than 20.9%, and moderate and marked goiter were independent variables associated significantly with a lower response rate (odds ratio 2.601, 4.023, and 3.309, respectively), whereas previous surgical treatment was associated with a higher response rate (odds ratio 3.071). No correlation was found between outcome and age, presence of exophthalmos, previous treatment with methimazole, and its duration. The response rate to the second dose was significantly increased compared with the first one by 27.8%; there was no correlation among the above-mentioned factors and its outcome. The third dose controlled the disease in 81.3% of the remaining patients and control was achieved in the rest after the fourth dose. (131)I is a very effective therapy for Graves' disease, with a cure rate of 100% after four doses. Higher first dose activity is recommended in the presence of poor prognostic factors. The second dose is not necessarily increased in the nonresponders.