Neonatal hyperbilirubinemia, or newborn jaundice, is a common condition caused by high bilirubin levels. Blood group incompatibility between mother and baby is a major cause. This study examined the link between different blood group incompatibilities and their management in newborns with jaundice.This prospective observational study included 190 neonates with hyperbilirubinemia requiring phototherapy. They were divided into two groups: control (blood group compatible) and case (blood group incompatible). Data on demographics, investigations, and management were collected.Blood group incompatibility was present in 36.3% of cases, primarily ABO (28.9%). Rh incompatibility and ABO + Rh incompatibility accounted for 5.3% and 1.6%, respectively. DAT was positive in 32.7% of ABO incompatible cases, with anti-B more prevalent. Neonates with ABO incompatibility had the highest mean total serum bilirubin (TSB) level (13.04 mg/dL) and the largest overall decrease in TSB (-33.77%).The mean phototherapy duration was significantly longer in cases (44.1 h) compared to controls (35.5 h). ABO incompatible neonates had a longer average phototherapy duration (42.32 h) compared to controls. However, ABO+Rh and pure Rh incompatible cases had highest phototherapy duration among cases. Moreover, within ABO cases, the mean phototherapy duration was higher in DAT-positive cases (46 h) compared to DAT-negative cases (40.2 h). Delivery mode, parity, and gender did not significantly influence phototherapy duration, but gestational age might play a role.Various blood group incompatibilities, beyond RhD, are significantly associated with hyperbilirubinemia requiring phototherapy. ABO incompatibility was the most common cause. Neonatal jaundice is linked to blood group mismatch, with ABO+Rh and pure Rh incompatibility requiring longer phototherapy. However, ABO incompatible cases had longer phototherapy in comparison to controls. Gestational age might influence phototherapy duration.