The IMx, AxSym, and Architect immunoglobulin M anti-HBc assay systems for detecting hepatitis B virus e antigen-negative chronic hepatitis B virus infection were compared. Despite good intra- and interassay coefficients of variation, significantly different values and low correlation (overestimation by AxSym and underestimation by Architect) were observed. Association and cutoff values for distinguishing patients with viral replication should be established for all methods.