Immunoglobulin G4-related disease (IgG4-RD) is characterized by elevated serum IgG4 levels, IgG4-positive plasmacytes, and lymphocyte infiltration into multiple organs. IgG4 thyroiditis is a subset of patients with Hashimoto’s thyroiditis (HT) who exhibited histopathological features of IgG4-RD; its source of serum IgG4 is suggested to be the thyroid gland. Although a relationship between IgG4-RD and IgG4 thyroiditis has been reported, the meaning of serum IgG4 in HT is uncertain. In this report, we prospectively evaluated serum IgG4 levels and clinical features of patients with HT. A total of 149 patients with HT were prospectively recruited into this study. According to the comprehensive diagnostic criteria of IgG4-RD, patients were divided into two groups: elevated IgG4 (>135 mg/dL) and non-elevated IgG4 (≤135 mg/dL). Median serum IgG4 levels of HT patients were 32.0 mg/dL (interquartile range, 20.0-65.0), with a unimodal non-normal distribution. Six patients (4.0%) had elevated serum IgG4 levels above 135 mg/dL. The elevated IgG4 group was older and exhibited enlarged hypoechoic areas in the thyroid gland, as revealed by ultrasonography, relative to the non-elevated IgG4 group. Levothyroxine (L-T4) replacement doses and titers of anti-thyroid antibodies did not differ significantly between the two groups. Two out of six HT patients with elevated serum IgG4 levels had extra-thyroid organ involvement as seen in IgG4-RD. In conclusion, HT patients with elevated serum IgG4 levels shared clinical features with both IgG4-RD and IgG4 thyroiditis. Longer follow-up periods and histopathological assessments are needed to further understand the meaning of elevated serum IgG4 levels in HT.