Introduction: Neonatal hyperbilirubinemia is a significant cause of morbidity among term neonates. Delayed follow- up of newborns may lead to considerable morbidity and encephalopathy. High bilirubin levels may necessitate exchange transfusion, especially in infants with ABO or Rh blood incompatibility. Measurement of Umbilical Cord Bilirubin (UCB) is an easily available, inexpensive and non invasive method to predict the development of hyperbilirubinemia in newborns. Aim: To determine the predictive value of UCB in estimating the risk of subsequent hyperbilirubinemia in term neonates with ABO incompatibility and to establish a UCB cut-off associated with the risk of hyperbilirubinemia development. Materials and Methods: This prospective cohort study was conducted at the Punjab Institute of Medical Sciences (PIMS) in Jalandhar, Punjab, India, from June 2022 to March 2023. A total of 113 term babies born to O+ mothers were included in the study. At the time of delivery, cord blood was drawn from the placental side of the cord for blood group, Direct Coomb’s Test (DCT), and serum bilirubin analysis. Infants were followed-up every 12 hours while inpatient and every 48 hours after discharge until day 5 for assessment of clinical jaundice. Significant hyperbilirubinemia was managed with phototherapy according to American Academy of Paediatrics (AAP) guidelines. The data was collected and subjected to statistical analysis using IBM Statistical Package for Social Sciences (SPSS) 20.0 software, with a significance level set at p-value <0.05, utilising Receiver Operating Characteristic (ROC) curve analysis. Results: A total of 113 term neonates were enrolled in the study, of which 57 (50.4%) were females. The mean cord bilirubin level was 2.6±1.06 mg/dL. A total of 40 (35.3%) babies developed significant jaundice requiring phototherapy, with a mean highest bilirubin level of 15±3.2 mg/dL. Using a cord bilirubin level of ≥2.0 mg/dL, significant hyperbilirubinemia could be predicted with a sensitivity of 80%, specificity of 54%, positive predictive value of 57.97%, and negative predictive value of 75%. There was a positive correlation between cord bilirubin and postnatal serum bilirubin in the present study, as determined by ROC analysis {Area Under Curve (AUC) >0.5}. Conclusion: The present study concluded that UCB is an important predictor of significant hyperbilirubinemia occurrence in newborns with ABO incompatibility.