There is controversy whether simultaneous thyrostatic medication influences the outcome of radioiodine (131I) therapy in Graves' disease by reducing the absorbed energy dose of 131I when delivering a standard dose. We therefore sought to ascertain whether the outcome of ablative 131I therapy is in any way affected by simultaneous thyrostasis (carbimazole) by aiming for a constant absorbed dose of 200-250 Gy. We prospectively studied 207 patients with Graves' disease (106 with and 101 without simultaneous carbimazole at the time of 131I therapy). All patients were reexamined 3, 6, and 12 months after 131I therapy. The 101 nonthyrostatic patients showed a highly significantly greater success rate (93%) than the 106 thyrostatic patients (49%). Stepwise logistic regression demonstrated that failure was related to the administration of carbimazole during 131I therapy (P < 0.00005) and the absorbed dose (P < 0.025), but was not related to free T3, free T4, TSH receptor antibodies, or thyroid volume. The success rate was 100% in 93 nonthyrostatic patients with absorbed doses of 200 Gy or more, but was only 12.5% (1 of 8) for absorbed doses less than 200 Gy. Correlation between success and absorbed dose was significantly higher for nonthyrostatic than for thyrostatic patients (r = 0.93 vs. r = 0.24). Sixteen patients who discontinued thyrostasis 1-3 days before 131I therapy showed 94% successes. Simultaneous thyrostasis is the decisive factor against a successful 131I therapy even if the significantly reduced 131I uptake/half-life values under thyrostasis are compensated with a higher delivered dose to ensure a comparable absorbed dose, possibly due to the additionally effective radioprotective properties of carbimazole. Therefore, if clinically feasible, we recommend discontinuing thyrostasis at least 1 day before beginning 131I therapy, because even in hyperthyroid nonthyrostatic patients the success rate was 100%.