Objective: Our objective was to evaluate the trend of antithyroglobulin antibodies (TgAb) during follow-up of patients with differentiated thyroid cancer (DTC) treated without RAI, as well as their role in the risk of recurrence. Subjects and methods: This was a prospective, descriptive study. A total of 152 consecutive patients with DTC treated in a single institution undergoing total thyroidectomy without RAI and followed for a median of 2.3 years (0.5-10.3) were divided in two groups: TgAb(-) (n = 111) and TgAb(+) (n = 41). Patients were classified according to AJCC 7 th and 8 th editions, as well as to their risk of recurrence and response to treatment categories. Results: Both groups, TgAb(-) and TgAb(+), were similar regarding patient and tumor characteristics. At the end of follow-up, 90 (59.2%), 57 (37.5%), 3 (2%) and 2 (1.3%) patients achieved excellent, indeterminate, biochemically incomplete and structurally incomplete response, respectively. The risk of structural recurrence was similar in both groups (TgAb[-] 0.9% vs. TgAb[+] 2.4%, p = 0.46). In the TgAb(+) group, TgAb became negative in 10 (24.4%), decreased ≥ 50% without negativization in 25 (60.9%), decreased < 50% in 4 (9.8%) and remained stable or increased in 2 (4.9%) cases. The only incomplete structural response had increasing TgAb during follow-up. Conclusions: In properly selected patients with DTC, TgAb concentration immediately after total thyroidectomy should not mandate RAI ablation, and their trend during follow-up may impact the risk of recurrence. Arch Endocrinol Metab. 2019;63(3):293-9