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Introduction: We aimed to characterize postpartum disease flares among treatment-naive mothers with chronic hepatitis B (CHB). CHB mothers were enrolled and compared with non-infected mothers in terms of postpartum alanine aminotransferase (ALT) abnormalities., Methods: Demographic, virological, and biochemical parameters were collected up to postpartum week 16, with flares and exacerbations defined as ALT levels 5-10 and >10 times the upper limit of normal, respectively. Outcome assessments included ALT flares or exacerbation and their predictive parameters., Results: Among 4236 patients enrolled, 869 and 3367 had no infection (group A) and had CHB (group B), respectively. Infected mothers were further stratified into two subgroups by the presence (B1, n = 1928) or absence (B2, n = 1439) of detectable serum levels of hepatitis B virus (HBV) DNA (lowest level of quantitation, 100 IU/mL). A significantly higher frequency of abnormal ALT levels was observed in group B vs. group A (28.27 vs. 20.37%, p < 0.001). ALT events mainly occurred in group B1 (flares, 115/1928, 5.96%; exacerbations, 57/1928, 2.96%). The ALT levels had a bimodal pattern, with peaks at postpartum weeks 3-4 and 9-12. On multivariate analysis, elevated ALT levels and detectable levels of HBV DNA at delivery were independent risk factors for postpartum disease flares. Further subgroup analysis in group B1 demonstrated that a cut-off HBV DNA level of 5 log 10 IU/mL at delivery predicted ALT events (positive predictive value, 14.4%; negative predictive value, 98.2%)., Conclusions: Postpartum ALT level elevation is common in CHB patients. ALT flares or exacerbations are mainly observed in mothers with elevated ALT or HBV DNA levels ≥5 log 10 IU/mL at delivery.