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Aim: Based on the response criteria of the 2015 American Thyroid Associations guidelines, our objectives were to determine the response rate when using a low dose of 131-I GBq in patients with low-risk differentiated thyroid cancer (LRDTC) and the influence of clinical and analytical variables on the prediction of complete response. Methods: We performed a multicentre and longitudinal study, including patients who were operated for LRDTC and who underwent radioiodine remnant ablation with a low-dose of 131-I. All patients were assessed at 6–12 months, and their status was classified as complete (excellent response) or incomplete response (structural incomplete, biochemical incomplete or indeterminate response). Various factors including age, gender, histology, tumour focality and size, stage, time from surgery to treatment, type of thyroid-stimulating hormone (TSH) stimulation, preablation serum thyroglobulin (pTg), antiTg antibodies (pAntiTgAb) and TSH (pTSH) levels were also analysed in order to predict the complete response rate. Results: Of 108 patients, 79.6% achieved complete response and the remaining showed incomplete response (2.9, 5.5 and 12% due to biochemical incomplete, structural incomplete and indeterminate response respectively). Six patients received a new dose of 131-I. Tumour size and pAntiTgAb were the only factors related to therapeutic response (p = 0.03 and p < 0.01, respectively). However, pAntiTgAb was the only independent factor related to complete response. Patients with complete response showed lower pTg than those with incomplete response (5.1 ± 12.9 vs. 11.2 ± 25 ng/mL) although without statistical significance (p = 0.14). There was no significant difference in the response rate depending on the thyrotropin stimulation methods. Conclusions: A low dose of 131-I was sufficient for reaching a complete response at 6–12 months of follow-up in the majority of patients with LRDTC. Tumour size and pAntiTgAb variables were related to therapeutic response.