Purpose The goal of the current study was to investigate the impact of different computational models on(131)I dosimetry prior to hyperthyroidism therapy. It was also aimed to highlight an accurate and cost-effective method for routine dosimetry of graves and toxic adenoma patients. Methods A cohort of 45 patients was recruited in the current study with Graves (n = 30) and Toxic Adenoma (n = 15) diseases. The eligibility criterion was determined using the patients' blood test,Tc-99m- pertechnetate scintigraphy, and ultrasound scan. A properly calibrated thyroid probe equipped with sodium iodide crystal [NaI(Tl)] was used to obtain the uptake measurements at 2, 24, 48, 72, and 96 h following administration of 0.27-0.73 MBq(131)I tracer. The absorbed radiation dose of the thyroid gland/nodule was calculated by three different methods. The calculation models were based on the time-integrated activity (recommended by MIRD), effective half-life (recommended by EANM), and ellipsoidal-shape assumption. Results The mean effective half-life was 138 +/- 41 h and 110 +/- 48 h in Graves and Toxic Adenoma patients, respectively. The mean residence time was 125 +/- 5 h in Graves patients, while it was 93 +/- 55 h in Toxic Adenoma. The amount of(131)I activity required to deliver 200 Gy to the thyroid gland in Graves patients was calculated as 436 +/- 381 MBq, 426 +/- 370 MBq, and 488 +/- 455 MBq according to MIRD, EANM, and ellipsoidal-shape model, respectively. However, the activity required to impart 300 Gy in the toxic nodules was computed as 622 +/- 332 MBq by MIRD, 907 +/- 588 MBq by EANM, and 1060 +/- 639 MBq by the ellipsoidal-shape model. Overall, no significant difference was found between the MIRD and both of the EANM and ellipsoidal-shape models in the Graves patients (R-2 = 0.99,P > 0.05). In contrast, less agreement (R-2 = 0.86) was shown between EANM and MIRD in Toxic Adenoma patients with no statistically significant difference (P > 0.05), while the difference was significant (P-value 0.05) between the MIRD and the ellipsoidal-shape model with moderate association (R-2 = 0.66). Conclusion It was deduced that the effective half-life-based model (EANM model) is a successful and affordable method for performing dosimetry in Graves patients. While, unit density sphere model sounds the most appropriate approach to be used in Toxic Adenoma dosimetry. However, using the ellipsoidal-shape assumption in the thyroid gland/or nodule dose calculation leads to redundantly larger activity administration.