Comparison between the different doses of radioactive iodine ablation prescribed in patients with intermediate-to-high-risk differentiated thyroid cancer Abstract Objective This study aimed to compare the clinical outcomes of patients who received radioactive iodine (RAI) ablation after undergoing thyroidectomy for intermediate-to-high-risk differentiated thyroid carcinoma (DTC) according to the American Thyroid Association (ATA) criteria. Methods We retrospectively examined patients who underwent RAI ablation for DTC after surgical resection without macroscopic residual lesions or metastatic lesions between December 2011 and August 2016. Among 147 patients who underwent RAI ablation, those whose initial pathological stages or RAI ablation results were unknown and whose distant metastases were confirmed during RAI ablation were excluded. Low-dose therapy was defined as administration of 1110 MBq of 131iodine (131I), while high-dose therapy referred to administration of 2960–3700 MBq of 131I. We defined initial success of RAI ablation as a serum thyroglobulin concentration of < 2.0 ng/mL without thyroid-stimulating hormone stimulation and disappearance of 131I uptake in the thyroid bed on 131I scintigraphy 6–12 months after RAI ablation. RAI ablation success rates were compared between the low-dose and high-dose groups using Fisher’s exact test, and inverse probability of treatment weighting (IPTW) analysis was performed for adjusting potential biases. Results Among the 119 patients examined in this study (39 men and 80 women), 79 were classified as having intermediate risk, while 40 were classified as having high risk based on the ATA guideline. Initial RAI ablation success was achieved in 50/68 (73.5%) patients from the low-dose group and in 36/51 patients (70.6%) from the high-dose group (p = 0.84). Moreover, IPTW analysis showed no significant difference between the low-dose and high-dose groups. However, the success rate tended to be superior in high-risk patients who received high-dose therapy (86.2%) than in those who received low-dose therapy (72.7%) (p = 0.37). Conclusion There was no significant difference in the RAI ablation success rate between the low-dose and high-dose groups involving patients with intermediate-to-high-risk DTC. However, high-dose RAI ablation may be recommended in high-risk patients.