SummaryThe mechanism of disease progression in Hashimoto's thyroiditis (HT) is still unclear. Anti-thyroid peroxidase antibody (TPOAb), a diagnostic hallmark of HT, is principally of the immunoglobulin G (IgG) isotype, and it appears to be a response to thyroid injury. The aim of our study was to evaluate the distribution of IgG subclasses of TPOAb in sera from patients with HT with different thyroid functional status. Sera from 168 patients with newly diagnosed HT were collected and divided into three groups according to thyroid function: patients with hypothyroidism (n = 66), subclinical hypothyroidism (n = 60) and euthyroidism (n = 42). Antigen-specific enzyme-linked immunosorbent assay was used to detect the distribution of TPOAb IgG subclasses. The prevalence of TPOAb IgG subclasses in all patients' sera with HT was IgG1 70·2%, IgG2 35·1%, IgG3 19·6% and IgG4 66·1% respectively. The prevalence of IgG2 in sera from patients with hypothyroidism (51·5%) was significantly higher than that of subclinical hypothyroidism (33·3%) (P < 0·05), and the latter was also significantly higher than that of euthyroidism (11·9%) (P < 0·05). The positive percentage of IgG2 subclass in sera from patients with hypothyroidism and subclinical hypothyroidism was significantly higher than that of euthyroidism (P < 0·05), the prevalence and positive percentage of IgG4 subclass in sera from patients with hypothyroidism and subclinical hypothyroidism was significantly higher than that of euthyroidism respectively (P < 0·05). The predominant TPOAb IgG subclasses in sera from patients with HT were IgG1 and IgG4. Patients with high levels of TPOAb IgG2, IgG4 subclasses might be at high risk of developing overt hypothyroidism.