Long-term studies evaluating the treatment of toxic multinodular goitre (TMNG) with fixed activities of radioiodine (RAI) are lacking.To describe the effects of 15 mCi on thyroid volume, function and autoimmunity in the long-term.and Setting: Population-based, retrospective analysis with up to 12 years of follow-up, held in Siena, Italy.Adult patients (n=153) with TMNG, naïve to RAI.Evaluation of thyroid function, anti-thyroid antibodies and ultrasound scans before and yearly after RAI.Hyperthyroidism cure, hypothyroidism; volume reduction, nadir and regain; antibody titre change.The study revealed mean volume reductions ≥50% 3 years after RAI, the greatest annual reduction was observed during the 1st year (30±17.8%; p<0.001). Most patients (60%) achieved their volume nadir 3-6 years after RAI. Although 22% patients showed volume regain, the net reduction was statistically significant as late as 9 years after RAI (p=0.005). The mean time to hypothyroidism was 2.7±2.4 years and it was associated with greater reductions in volume (p=0.013). During the 1st 3 years after treatment, hyperthyroid patients decreased approximately by 50%/year without additional RAI. There was no statistically significant association of antibody titres with thyroid function except for TRAb and hyperthyroidism (p=0.004). At the end of follow-up there were 61.6% euthyroid patients, 11% hyperthyroid (4.8% overt) and 27.4% hypothyroid patients (2.7% overt). Hyperthyroidism was cured in 89%.The treatment of TMNG with 15 mCi of RAI induced low hypothyroidism rates while providing high cure rates and significant volume reduction, maintained in the long-term.