Aim: to determine the cord blood nucleated RBCs as a potential tool in prediction of neonatal hyperbilirubinemia in ABO incompatibility susceptible neonates. Material and methods: This prospective study was done the Upgraded Department of Paediatrics, Patna Medical College & Hospital, Patna, Bihar, India, from August 2015 to November 2016. Total 120 consecutive healthy term babies born to O+ve mothers were included in this study. Cord blood was collected for estimating blood group, bilirubin and DCT for all babies born to O+ve blood groups. The study population was initially followed up for first 5 days of life clinically by Kramer’s method. Newborns identified with jaundice were followed up. using serial serum bilirubin values. Two ml of venous blood sample was collected in plain vial from the baby on day 5th of life or earlier if clinically indicated. Serum bilirubin was estimated using diazo method. Results: Out of 120 newborns, 20 (16.67%) newborns developed jaundice and were classified as significant hyperbilirubinemia and 100 (83.33%) who did not developed jaundice were grouped as non- hyperbilirubinemia. Among 20 newborns who developed significant hyperbilirubinemia, 65 % newborns were from 2.5- 3.00kg birth weight (p value 0.529). Most common blood group associated with ABO incompatibility leading to significant hyperbilirubinemia was B+ (80 %) followed by A+ (15 %) and AB + (5%) (p value <0.01). 75% newborns who develop significant hyperbilirubinemia were early term (37-38 weeks) (p value <0.05). 55 % newborns who developed significant hyperbilirubinemia were delivered by LSCS (p value 0.84). There was no significant difference in the number of male (60%) and female (40 %) babies developing significant hyperbilirubinemia (p value <0.81). Mean cord bilirubin of newborns that developed significant hyperbilirubinemia was 2.27 with SD of 0.68. Significant hyperbilirubinemic newborns were distributed according to development of hyperbilirubinemia as before 5th day (clinically observed) 12 (60 %) and on day 5th 8 (40%). Conclusion: Cord blood total bilirubin levels ≥1.79mg/dl has a good predictive ability for prediction of significant hyperbilirubinemia among ABO incompatible new-born. DCT is neither specific nor sensitive screening tool for development of Neonatal hyperbilirubinemia in ABO incompatibility.