Background and Aims Jaundice is one of the most common problems in newborn period. İnfants at risk for severe hyperbilirubinemia should be identified and closely monitored in order to avoid kernicterus. This study was performed to identify the etiology and sociodemographic characteristics of newborns with severe indirect hyperbilirubinemia who had exchange transfusion. Methods The study sample included all infants who were undergone exchange transfusion at Adnan Menderes University NICU from January 2000 through December 2010. Hospital records were reviewed. Blood groups, direct Coombs test, whole blood count, peripheric blood smear, CRP, reticulocyte count, total, direct bilirubine levels, Tandem mass, G6PD and pyruvate kinase levels, urinalysis and urine culture, reducing substance in urine were investigated. Results Sixty-five of the patients were male, 26.5% preterm. Mean gestational age was 39.3±1.4 for term infants, 35±1.1 weeks for preterms. Mean serum total bilirubin level was 25±6.3 mg/dl. Twenty- four % of the patients had Rh incompatibility, %24.5 had ABO incompatibility, 6.1% had both Rh and ABO incompatibility,%4.1 G-6-PD deficient, 12.2% had early breast milk jaundice, % 12.2 had sepsis, 6.1% had hemolysis of unknown etiology. In five babies no etiology was discovered. Conclusions Most of the infants had Rh or ABO incompatibility, who were vaginally delivered, discharged within 24 hours of birth and exclusively breastfed. Since mean age at admission was 3.4±3.7 days, serum total bilirubin levels should be measured before discharge and discharge should be delayed in high risk babies.