Background: Haemolytic disease of the newborn is often secondary to ABO incompatibility, the routine practice of early discharge of newborns leads to a higher occurrence rate for hyperbilirubinemia. We aim to compare the probability of ABO incompatibility and the prevalence of ABO haemolytic disease of the newborn (ABO HDN) and investigate the clinical characteristics of ABO HDN to identify risk factor for ABO HDN. Procedure: The blood type of 85 590 blood donors and the inpatient medical records of 471 ABO HDN were analysed retrospectively. Results: The possibility of a blood group O woman giving birth to a non-group-O infant should be 13.28%; however, only 6.03% of newborns had ABO HDN. 49.46% of total ABO HDN newborns developed disease due to anti-A antibody and 50.54%, due to anti-B. No significant difference was found in group A and B newborns in haemoglobin and peak total serum bilirubin (TSB) levels, but lower haemoglobin values were observed in ABO HDN infants with a positive direct anti-globulin test (DAT). Furthermore, the correlation coefficient between the postnatal age of admission and peak TSB levels was 0.54. When severe hyperbilirubinemia developed, the peak TSB levels increased gradually with the increase in postnatal age of admission. Conclusion: For ABO-incompatible mother-infant pairs, timely monitoring is advised, since early hospitalization and appropriate interventions, if necessary, can reduce the risk of severe hyperbilirubinemia, especially for DAT-positive newborns.