Objective: This study aimed to investigate the long-term effect of radioiodine (RAI) treatment on thyroid functions and ultrasonographic changes in the thyroid gland and toxic nodules. Methods: Thyroid function tests and ultrasonography reports of patients diagnosed with toxic adenoma (TA) or toxic multinodular goitre (TMNG) between 2000 and 2021 were retrospectively analysed. Results: We included 100 patients whom thyroid function and ultrasonography results were obtained from our outpatient clinic before and at least 36 months post-RAI. At the end of the follow-up period, the mean thyroid volume reduction in patients with TA and TMNG was 56.6% ± 3.1% and 51.1% ± 6.7%, respectively; the mean volume decrease of all toxic nodules was 80.5% ± 1.9%. The volume of the thyroid and toxic nodules was significantly reduced up to 12 years (p < 0.01). Between 3 and 10 years after RAI therapy, the annual incidence of hypothyroidism was 2.0% and 1.5% in the TA and TMNG groups, respectively. Toxic nodules were more frequently solid and hypoechoic in post-RAI ultrasounds (p < 0.01). Conclusions: The volume of thyroid gland and toxic nodules continuously decreases, as the risk of hypothyroidism increases up to 10 years after RAI treatment. After RAI treatment, patients should be followed up to check their thyroid functions. In post-RAI examinations, toxic nodules may show ultrasonographic features suspicious for malignancy. History taking should include previous RAI therapies and old scintigraphy scans should be evaluated to avoid unnecessary procedures and non-diagnostic biopsy results.