BACKGROUND Better understanding of the clinical characteristics of ABO haemolytic disease in neonates helps optimise care. OBJECTIVE To assess the morbidity associated with maternal-neonatal ABO incompatibility. METHODS Neonates with blood groups A or B born to mothers with blood group O with simultaneous rhesus blood factor compatibility were studied prospectively. Maternal and neonatal details, direct Coomb's test (DCT) on the cord blood, onset and progression of jaundice, and requirement and duration of phototherapy were studied. Neonates requiring phototherapy were considered to have significant hyperbilirubinaemia, and peripheral smear, reticulocyte count and haematocrit values were obtained. ABO haemolytic disease of the newborn (ABO HDN) is defined as a newborn with a positive DCT and/or laboratory evidence of haemolysis such as reticulocytosis and spherocytes on blood smear. RESULTS Of 878 deliveries, 151 (17.3%) neonates were ABO incompatible with their mothers. The proportions who were O-A and O-B incompatible were 50.4% and 49.6%, respectively. Forty-six (30.4%) had significant hyperbilirubinaemia (119.7-256.5 mmol/L) and required phototherapy, 26 (34.2%) of them in the O-A group and 20 (26.6%) in the O-B group. None required exchange transfusion. Jaundice was detected within the first 24 hours in 47.8%. Of 46 newborns who required phototherapy, 25 (54.3%) had laboratory evidence of haemolysis. DCT was positive in 1.9% of ABO-incompatible newborns. There was no significant difference in the incidence and severity of haemolysis between the O-A and O-B-incompatible neonates. Neonates with haemolysis required phototherapy significantly earlier and for longer than neonates without haemolysis (P<0.001). CONCLUSIONS ABO incompatibility was observed in 17.3% of pregnancies with almost equal O-A and O-B frequency. About a third of infants had significant hyperbilirubinaemia. There was no difference in severity between those with O-A and O-B HDN.