Treatment of Graves disease (GD) with antithyroid drugs (ATD) leads to remission of the disease in approximately half of patients treated for at least 6 months and the overall relapse rate is high. A few small prospective trials have considered methimazole (MMI) somewhat more effective and safer in lower doses than propylthiouracil (PTU), but the choice between the drugs has been a matter of personal preference. The aim of this clinical trial is to evaluate the effect of different ATD regimens on remission rates of GD and on the side effect profiles. The study included 55 previously untreated patients with GD who were randomized in 2 groups: 40 to 60 mg methimazole daily was prescribed to 30 patients and 200 to 300 mg propylthiouracil every 12 hours was prescribed to 25. The patients were treated for 12 months and followed for 12 to 38 months after drug withdrawal. Fifteen patients of 21 in the PTU group (71.4%) and 10 of 25 in the MMI group (40.0%) reached 1-year remission of GD (P = 0.04), but there was no statistical difference between the drug regimes after adjusting for antithyroid-stimulating hormone receptor antibody (TRAb) levels. Among the 25 patients who reached 1-year remission, relapse occurred in one case at 18 months after drug withdrawal. All patients presented good compliance and only 2 patients developed minor side effects. During the treatment, both drug groups showed a significant fall in serum TRAb and thyroid peroxidase autoantibody titers, and the TRAb levels observed in the MMI group were consistently higher. Therefore, in our study, there were no significant differences between PTU and MMI groups in relation to remission rate, side effect profiles, and compliance rates. Furthermore, individuals with higher baseline antibody titers presented a lower probability of long term remission of GD.