BACKGROUND Hepatitis B virus (HBV) infection is one of the infections with a highest prevalence in Taiwan. The most important marker is hepatitis B surface antigen (HBsAg). Using the new generation of HBsAg quantitative assay, HBsAg level may have good correlation with viral activity during different phases of chronic hepatitis B virus infection. This study was conducted to compare two assays of HBsAg level to find if the same results are obtained in HBsAg quantification in treatment-naïve and on-treatment chronic hepatitis B patients. METHODS Between March 2012 and June 2012, 90 patients with chronic hepatitis B (68 males and 22 females) were assessed using Abbott Architect HBsAg QT and Roche Elecsys HBsAg II assay. HBV DNA was detected by Roche COBAS TaqMan instrument. RESULTS HBsAg level measured with Elecsys and Architect assays correlated well in untreated patients (n = 53, γs = 0.997) and on-treatment patients (n = 37, γs = 0.988). Bland-Altman analyses of the discrepancies in HBsAg levels showed a bias of -4.2% in untreated patients and -6.2% in on-treatment patients. Patients with HBeAg-postive chronic hepatitis B had higher HBsAg level than the ones who were HBeAg negative, and both showed statistical differences. Further, HBV DNA concentration analysis also showed higher viral concentration in HBeAg-positive patients, but it revealed no statistical difference. CONCLUSIONS There is a significant correlation between Abbott Architect HBsAg QT assay and Roche Elecsys HBsAg II assay. Moreover, HBsAg quantification may potentially provide complementary information about the deduction of the natural course in chronic hepatitis B infection.