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Background: This study aimed to compare the effectiveness and safety of radioiodine (RAI) and long-term methimazole (MMI) in the treatment of subclinical hyperthyroidism (SH) in the elderly. Methods: From 306 patients, aged ≥65 years, with SH, 83 patients with thyrotropin <0.1 mU/L entered the study. In this randomized parallel-group trial, 41 and 42 patients were randomized to either RAI or long-term MMI treatment, respectively. Results: In the RAI and MMI groups, 3 and 4 patients were excluded due to side effects, choosing other modes of treatment, and not returning for follow-up; 35 and 36 patients completed 60 months of follow-up, respectively. In the RAI group, 23 (66%) became hypothyroid, and 12 (34%) remained euthyroid 60 months after a fixed dose of 15 mCi RAI. In the MMI group, the starting dose was 10 mg daily and decreased to 4.9 ± 1.0, 4.3 ± 1.0, 4.4 ± 1.4, 4.3 ± 1.8, and 3.7 ± 1.3 mg after 1, 2, 3, 4, and 5 years of continuous MMI treatment, employing titration method. By the end of study, 34 (94%) patients were euthyroid and 2 patients with diffuse goiter developed spontaneous hypothyroidism with MMI treatment. Minor adverse events occurred in both groups in the first four months of treatment. No death or serious side effects were observed during 60 months of follow-up. Conclusions: Both RAI and long-term low-dose MMI therapies are effective and safe for treatment of SH in the elderly. [ABSTRACT FROM AUTHOR]