Jaundice is one of the most common physiologic problems requiring medical attention in the newborn. Phototherapy and exchange transfusion remain the primary treatment modalities to keep the maximal total serum bilirubin below the pathologic levels. Aim of the work: To evaluate cases of neonatal hyperbilirubinemia admitted into the neonatal intensive care unit (NICU) of Cairo University Pediatric Hospital (CUPH) as regards the number of cases, causes, different management strategies and the outcome. This was in a trial to assess the magnitude of this common neonatal problem in our NICU. Methods: Retrospective observational study done in the NICU of CUPH on all neonates suffered from neonatal hyperbilirubinemia admitted to the NICU of CUPH over a two-year period from the start of January 2010 to the end of December 2011. Results: ABO incompatibility was the most common cause of jaundice in 42.5% of the cases, followed by unidentified cause in 38.5% then Rh incompatibility in 8% then sepsis in 7%. Sepsis or respiratory distress (as an association) significantly worsened the outcome of neonatal jaundice (P<0.001 for each). Rh incompatibility significantly worsen the outcome (P=0.005), while ABO incompatibility did not significantly affect the mortality among cases (P=0.11). Average duration of hospital stay for cases used intensive phototherapy (Bilisphere) was 3.81 days, while it was 5.21 days for cases used the other methods. Conclusion: Neonatal hyperbilirubinemia is an existing problem in our NICUs related to many etiological factors and associated with adverse outcome in the form of neurotoxicity up to death. Phototherapy was the mostly used mode of therapy and proved that intensive phototherapy reduces the need for exchange transfusion and thus the dangerous side effects of exchange can be avoided.