BACKGROUND AND OBJECTIVE. Current treatment options of Graves' disease (GD) are often unsatisfactory. This study aimed at determining the independent baseline predictors of medical treatment failure in GD. MATERIAL AND METHODS. A retrospective study of 194 patients with GD was carried out. According to the disease outcome, patients were divided into groups. The remission group included the patients who achieved long-term remission after initial antithyroid drug (ATD) treatment with no relapse (group 1) or after 2 or 3 courses of ATD therapy (group 2). The treatment failure group included the patients who underwent thyroid ablation due to relapse (group 3) or without ATD withdrawal (group 4). RESULTS. A family history of thyroid disorders was associated with greater odds of failure (P=0.046). Higher thyrotropin receptor antibodies (TRAb) levels and a larger goiter size (grade 2/grade 3) at the onset of the disease were both independently associated with a greater likelihood of failure. The initial TRAb concentration of 30.2 U/L and the TRAb concentration of 12.97 U/L at the end of ATD therapy were found to be the best cutoff values predicting the treatment failure. A hypoechogenic thyroid after ATD therapy, but not before therapy, increased the likelihood of failure by nearly 7.5 times (P<0.001). CONCLUSIONS. Higher TRAb levels and a larger goiter size at the onset of the disease were found to be the independent predictors of medical treatment failure in GD.