Aim: To evaluate the usefulness of cord blood analysis in predicting hyperbilirubinemia in babies at risk of Rh And Abo incompatibility. Material And Methods: The present hospital-based prospective observational study was conducted at Jaipur National Hospital, Jaipur among 100 babies born to O+VE or RH-VE mothers, delivered by both cesarean and natural labor from August 2022 to January 2024. The newborns detected to have pathological hyperbilirubinemia were furtherinvestigated by doing a Direct Coomb test, complete blood count, reticulocyte count andperipheral smear and were managed according to standard protocols as per guidelines ofthe American Academy of Pediatrics subcommittee on hyperbilirubinemia. Results:43% of cases are related to RH incompatibility, while 57% of cases are related to ABO incompatibility.18% of newborns had pathological jaundice. In the ABO and Rh incompatibility groups, clinical jaundice was observed in 52.63% and 27.91% of neonates, respectively.When significant hyperbilirubinemia was present as compared to absent, there was a significantly higher mean Cord bilirubin total.≥1.715 was the optimal cut-off for the value of Cord bilirubin - Total to predict significant hyperbilirubinemia, (AUC = 0.786) with a Sensitivity and Specificity of 85.7% and 56.9% respectively. Less than or equal to 16.5 gm/dl was the optimal cut-off value of Hb, (AUC = 0.831) with a Sensitivity and Specificity of 47.6% and 98.2% respectively. ≥0.21 was the optimal cut-off value of reticulocyte count to predict significant hyperbilirubinemia, (AUC = 0.675 ) with a Sensitivity and Specificity of 97.6% and 23.2 % respectively Greater Than or Equal to 2.7 was the optimal cut-off value of reticulocyte count to predict significant hyperbilirubinemia, (AUC = 0.793) with a Sensitivity and Specificity of 76.2% and 73.2% respectively. These values can be used as safe risk demarcations in deciding about the time of discharge of ABO-incompatible newborns from the hospital. Conclusion:It can be concluded from the results that cord bilirubin, haemoglobin, reticulocyte count and positive direct antiglobulin test are good predictors for significant hyperbilirubinemia and severe hemolytic disease.