The amount of 131I necessary for successful ablation in patients with differentiated thyroid cancer (DTC) is still subject to debate. This study investigates the relationship of the absorbed dose of radiation to the blood while administering 131I activity with several other parameters in DTC patients. This prospective study included 90 DTC patients who were classified into three groups according to their level of dosage: 3.7 GBq (38.9%), 5.55 GBq (55.6%), and 7.4 GBq (5.5%). Blood dosimetry of treated patients was performed using external whole-body counting with a Geiger Muller dosimeter located 2 m away from the patients. Dose rate was measured at 2, 4, 5, 24, and 48 h after the administration of radioiodine. Based on the results of whole-body dose rate measurements, 48 h after administration of 3.7, 5.55, and 7.4 GBq of radioiodine, absorbed doses to patients’ blood were estimated at 0.49 ± 0.12, 0.71 ± 0.21, and 0.76 ± 0.11 Gy, respectively. Increasing radioiodine dosage from 3.7 GBq to 5.55 GBq significantly increased blood dose, while there was no significant difference in blood dose between radioiodine dosages of 5.55 GBq and 7.4 GBq. The absorbed dose to the blood was significantly correlated to the patients’ gender and the presence of lymph node metastases, but it was not significantly correlated to the type of pathology and regional or distant metastases. Ablation activities exceeding 5.55 GBq produce no further increase in the accumulated activity per volume of blood. The literature regarding this issue is scarce, and further studies are required to verify these preliminary results.