BACKGROUND Inactive and active phases of hepatitis B e antigen-negative chronic hepatitis B virus (HBV) infection are diagnosed by serum HBV DNA levels, with cutoff at 2000 IU/mL. However, it is difficult to distinguish inactive carriers at a single time point because HBV DNA levels can transiently decrease to <2000 IU/mL even in noninactive carriers. OBJECTIVE We aimed to establish the role of serum hepatitis B surface antigen (HBsAg) in identifying "true inactive carriers" among treatment-naive genotype C HBV-infected patients with low viremia. METHODS A total of 133 hepatitis B e antigen-negative carriers with serum HBV DNA levels of <2000 IU/mL and normal alanine aminotransferase levels were enrolled and followed up for >12 months. RESULTS Forty patients (30.1%) were classified as noninactive carriers (HBV DNA ≥2000 IU/mL and/or alanine aminotransferase >40 IU/L) during 12 months from enrollment. No baseline serum HBV DNA levels could identify true inactive carriers with 100% specificity, whereas baseline serum HBsAg levels (50 IU/mL) identified true inactive carriers with 100% specificity and 29% detection rate. Detection rate increased when different cutoff levels were applied to different age groups according to median age (46 y). It was comparable in both younger and older groups (37.2% vs. 38%) even when HBsAg cutoff level was increased in the former (400 vs. 50 IU/mL). Furthermore, none reversed to noninactive phase during long-term follow-up when these cutoff levels were applied. CONCLUSIONS Baseline serum HBsAg levels at a single time point can identify persistently true inactive carriers, with different cutoff levels according to age.