SummaryIn radioiodine therapy of benign thyroid disease, a reduction of radioiodine uptake is known for consecutive administrations of 131I, which needs to be considered in therapy planning. Aim: Analysis of uptake reduction with regard on the time interval between radioiodine administration and the delivered dose to the thyroid tissue. Patients, methods: 200 patients were enrolled in the study and distributed into two groups (matched for diagnoses), each containing 32 patients with Graves' disease (target dose 250 Gy), 24 with focal (400 Gy), 44 with disseminated thyroid autonomy (150 Gy). In one group, a second fraction of radioiodine was given after 48 h (2d) due to an unexpected low radioiodine uptake or effective half-life, whereas in the other group the second fraction was given after 96 h (4d). Results: There was no significant difference between delivered doses due to the first fraction after four days: 2d: 86 ± 48 Gy (extrapolated) vs. 4d: 87 ± 41 Gy, p > 0.05. In 2d, delivered dose at time of second administration was significantly lower (51 ± 29 Gy) than in 4d (p < 0.01). The radioiodine uptake of the second fraction relative to the initial uptake was significantly lower in the 4d (4d: 63 ± 25% vs. 2d: 82 ± 24%, p < 0.01). In addition, a correlation between uptake reduction and delivered dose and an influence of the time interval between radioiodine administrations could be shown. Conclusions: Relative uptake of subsequent radioiodine fractions decreases with time after first administration and with increasing delivered dose to the thyroid. If a second fraction of 131I is given at an earlier time, the same therapeutic effect can be reached using lower amounts of activity, minimising radiation exposure and increasing efficiency of radioiodine therapy.