Background and Importance: Surgical practices in thyroid oncology recently evolved towards de-escalation, with more frequent 2-step surgery (lobectomy then totalisation). Moreover, in non-metastatic thyroid cancers with low risks of recurrence, radioiodine therapy (RIT) to eliminate potential residual cancer cells has become optional, particularly in cases displaying low postoperative thyroglobulin (POTg) values. It is known that plasma thyroglobulin is correlated with the size of the post-thyroidectomy residue, excluding distant metastases. However, it is not known whether this residue is greater in the case of 1- or 2-step surgery. Indeed, the 2-stage approach may provide a more substantial residue, measurable by the POTg value. Clinicians should therefore take this notion into consideration when deciding on adjuvant RIT. Aim and Objectives: To compare POTg values in patients undergoing 1- or 2-step thyroidectomy for low-risk thyroid cancer, based on retrospective collection of biological data from operative and pathological reports in a cohort of RIT patients at our centre. Material and Methods: Inclusion criteria for this study were: non-metastatic patients with a low-risk pathology who had biological tests performed between surgery and RIT consultation, a non-detectable anti-thyroglobulin antibody assay, a period >28 days between surgery and biological tests, and TSH levels <5 µIU/mL. Parameters useful for describing the patient population and comparing POTg values were compiled in a computerised spreadsheet and analysed. Results: Between 15 July 2016 and 24 February 2023, 70 patients from our centre met the inclusion criteria. Mean TSH value was 1.377 ± 1.336 µIU/mL and mean POTg was 0.543 ± 1.067 ng/mL. Mean time between operations for patients treated in 2-steps was 82 ± 55 days and mean time between operation and biological test was 68 ± 54 days. Two groups were defined, including 49 patients who underwent 1-step surgery and 21 patients who underwent 2-step surgery. Difference between the two groups in mean TSH values and average time between operation and biological test were not statistically significant (p = 0.204 and 0.97, respectively). No statistically significant difference could be demonstrated between the mean POTg in the two groups (p = 0.622). Conclusion and Relevance: Mean POTg appears to be independent of the surgical procedure, which is an important consideration when deciding on postoperative treatment.