Objective:To observe the efficacy of methimazole (MMI) combined with 1α-hydroxyvitamin D3 (alfacalcidol, ALF) in patients with Graves disease of high-titer thyrotropin receptor antibodies (TRAb) and to explore new clinical strategies to reduce serum TRAb in Graves disease.Methods:120 patients with Graves disease initially diagnosed in Quanzhou First Hospital Affiliated to Fujian Medical University and the People′s Hospital Affiliated to Quanzhou Medical College from June 2017 to June 2019 were prospectively selected as the research objects. All patients received conventional dose of MMI for anti hyperthyroidism treatment. The patients were randomly divided into three groups: group A [ n=40, treated with MMI combined with high-dose ALF (0.5 μg/d)], group B [ n=37, treated with MMI combined with low-dose ALF (0.25 μg/d)] and group C ( n=43, treated with MMI only). The treatment lasted for 24 weeks. The serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH) and TRAb in patients before and after above treatments were detected. The blood routine, liver function, alkaline phosphatase (ALP), 25(OH)D, serum calcium (CA) and serum phosphorus were detected regularly. Results:After drug treatment: ⑴ the thyroid function of the three groups returned to normal. The average daily dosage of MMI in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05), with significant difference. After 24 weeks of treatment, the daily dosage of MMI in group A and B was significantly lower than that in group C ( P<0.05). ⑵ There was no significant difference in thyroid function among the three groups. The concentration of serum TRAb in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05). ⑶ During the 24 week follow-up, there was no significant difference in serum 25(OH)D, ALP, Ca and P among the three groups ( P>0.05); no leukopenia in peripheral blood and no abnormal liver function were found in the three groups. Conclusions:MMI combined with ALF can effectively treat Graves′ disease, reduce the dosage of MMI drugs, decline the level of TRAb in the serum of Graves′ patients, and improve the prognosis of Graves′ disease.