Aim of this study was to determine whether success of radioiodine therapy (RIT) in Graves' disease depends on thyroid volume, function, thyroideal receptor antibodies (TRAK), thyreostasis, therapeutic dosage, I-131 uptake, or effective half-life. Method: 78 patients received an average of 626 +/- 251 MBq of iodine-131 orally for thyroid ablation. 60 were assessed for successful therapy 3 months after RIT. Results: In patients showing hyperthyreosis or a TRAK value > 11 U/I at the beginning of RIT, a significantly lower therapeutic dosage and effective iodine half-life were found than in non-hyperthyreotic patients or patients with TRAK less than or equal to 11 U/I. Patients with a thyroid volume less than or equal to 25 ml showed a significantly lower I-131 uptake, but: a significantly higher relative uptake (I-131 uptake/volume) than patients with a thyroid volume > 25 ml. All failures were treated thyreostatically during RIT and showed a significantly lower therapeutic iodine dosage and relative uptake, as well as a significantly higher thyroid volume than patients with a successful therapy. RIT caused a thyroid volume reduction of 44%, with therapy failures showing a significantly lower volume reduction. Patients who received a therapeutic dosage of less than or equal to 250 Gy showed significantly worse results than did those who had received > 250 Gy. Only one case of therapy failure received a dosage > 250 Gy, while 50% of failures received dosages > 200 Gy but < 250 Gy. Multivariate analyses (MANOVA, factor analyses) showed thyreostasis as the decisive negative factor for a successful course of therapy. Conclusions: Since most treatment failures occurred in patients under thyreostatic medication, we recommend raising the target dosage to 250 Gy for these cases.