Background: Low doses of antithyroid drugs (ATD) for extended periods may be an alternative for Graves' disease (GD) patients who relapse after a course of ATD. Methods: Patients with GD relapse (n=238) after discontinuation of ATD therapy for 12-24 months were retrospectively analyzed in a nonrandomized study. Radioiodine (RAI) treatment and L-thyroxine replacement was used in 114 patients, and a low dose of methimazole (MMI; 2.5-7mg/daily) was used in 124 patients. Thyroid dysfunction, Graves' ophthalmopathy (GO) evolution, quality of life (QoL), and body weight were evaluated during the follow-up. Results: The mean follow-up was 80.835.3 months for the RAI group, and 71.3 +/- 40.3 months for the low-dose MMI group. No notable side effects were observed in either group. Thyroid dysfunction was predominant in the RAI group (p<0.001), and euthyroidism was more common in the MMI group (p<0.001). GO deterioration was mainly evaluated by clinical activity score (CAS)it was higher in the RAI group (p<0.0005) over all periods of follow-up. Multivariate logistic analysis showed that RAI treatment was associated with no improvement in CAS during follow-up (24 months: OR=3.51 [CI 1.02-12.03], p<0.05; 36 months: OR=8.46 [CI 1.47-48.58], p<0.05; 48 months: OR=19.52 [CI 1.70-223.10], p<0.05; 60 months: OR=21.1 [CI 1.5-298], p<0.05). Kaplan-Meier survival analysis confirmed this finding (p<0.0003). Assessment of QoL using the Short Form Health Survey's 36 parameters in stable euthyroid patients (at least six months) was similar in both groups. The RAI group patients gained more weight (p<0.005), particularly after 24 months of follow-up. Conclusions: The use of low doses of MMI is efficient and safe, and offers better outcomes for GO than RAI treatment. Prolonged low doses of MMI may be an alternative choice for relapsed GD patients, particularly for GO patients or for patients who refuse a definitive treatment.2512 12821290