Autoimmunity is not believed to be involved in tissue damage of Β-Thalassemia (Β-Thal), although nonspecific triggering of autoimmunity by iron overload has been suggested. We recently re-evaluated thyroid function and autoimmunity in 132 Β-Thal patients born and living in Sardinia Island, where a high prevalence of both Β-Thal and autoimmune disease is well documented and in 1002 age and sex-matched euthyroid individuals from the general population. The prevalence of primary hypothyroidism in Β-Thal patients was 28.7% (38/132), without significant difference between males (M) and females (F). Hypothyroidism was associated with smaller and hypoechoic glands, while no difference in the prevalence of anti-thyroid antibodies (ATA) was found between Β-Thal patients with or without thyroid failure. Interestingly, the prevalence of ATA in Β-Thal women (9.2%) was significantly lower than that found in age-matched euthyroid women (20.0%). Our study confirms that thyroid autoimmunity has no role in the pathogenesis of hypothyroidism in b-Thal. Moreover, the lower ATA prevalence in Β-Thal women suggests that iron overload may inhibit rather then trigger thyroid autoimmunity.