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The aim of this study was to assess the efficacy of mean radioiodine activities of 12.6 MBq/mL in order to achieve a successful treatment of hyperthyroidism with a single radioiodine dose and a low incidence of hypothyroidism. We evaluated 51 patients with Plummer disease, 41 patients with multinodular toxic goiter, and 9 patients with compressive toxic and nontoxic goiter, after a short suspension of antithyroid drugs, with the exclusion of patients with critical cardiovascular conditions, an expanded iodine pool, and a nodular volume larger than 120 mL. Target volume was measured by ultrasonography and calculated by the ellipsoid method. All the patients underwent a thyroid uptake test with 1.85 MBq of ¹³¹I and measurements on the neck and thigh at 2, 6, and 24 hours. Target volume was 21.5 ± 21.4 mL for group 1, 15.4 ± 10.7 mL for group 2, and 56.4 ± 12.8 mL for group 3. The 24 hours uptake (mean % ± standard deviation) was 43.1 ± 19.9, 48.5 ± 15.4, 56.4 ± 12.8, respectively, for groups 1, 2 and 3. Mean follow-up was group 1: 23 ± 17 months; group 2: 23 ± 14 months; and group 3: 28 ± 20 months. First approximation dosimetry took into account thyroid volume and the 24-hour uptake percentage. A euthyroidism condition was reached in 40 of 51 patients (78.4%) of group 1, 35 of 41 patients (85.4%) of group 2, and 6 of 9 patients (66.7%) of group 3. Hypothyroidism was observed in 13 of 101 patients (12.9%). Only 9 of 101 (8.9%) patients were subclinically hyperthyroid at the end of follow-up. The over-all efficacy of treatment was 91.1%. Reduction (%) of nodule volume was 66 ± 23, 57 ± 18, and 79 ± 13, respectively, in groups 1, 2, and 3, with scintigraphic disappearance of hot nodules or persistence of cold nodules with the recovery of extranodular thyroid tissue in 76 patients.