Objective We investigated if a positive thyroid peroxidase antibody (TPO Ab) status before radioactive iodine (RAI) therapy in patients with Graves' hyperthyroidism is a predictive factor for developing hypothyroidism post RAI. MethodsWe performed a retrospective study of patients with Graves' hyperthyroidism with known TPO Ab status, receiving a first administration of RAI. Patients from 4 thyroid outpatient centres in Belgium receiving a first RAI therapy between the years 2011 and 2019 were studied.Clinical, laboratory, imaging, and treatment data were recorded from medical charts.Hypothyroidism and cure (defined as combined hypo-and euthyroidism) were evaluated in period 1 (≥2 and ≤9 months, closest to 6 months post RAI) and period 2 (>9 months and ≤ 24 months post RAI, closest to 12 months post RAI). ResultsOne hundred fifty-two patients were included of which 105 (69%) were TPO Ab positive.Compared to TPO Ab negative patients, TPO Ab positive patients were younger, had a larger thyroid gland, and had more previous episodes of hyperthyroidism. In period 1, 89% of the TPO Ab positive group developed hypothyroidism versus 72% in the TPO Ab negative group (p=0.007). In period 2, the observation was similar: 88% vs. 72% (p=0.019). In the multivariate logistic regression analysis, a positive TPO Ab status was associated with hypothyroidism in period 2 (adjusted OR 4.78 (95% CI 1.27-20.18;p=0.024). In period 1, the aOR was 4.16 (95% CI 1.0-18.83; p=0.052). ConclusionA positive TPO Ab status in patients with Graves' hyperthyroidism receiving a first administration of RAI is associated with a higher risk of early hypothyroidism.