Our goal was to determine the indications for exchange transfusion (ECT) and the rates of ECT-related adverse events in neonatal hyperbilirubinemia. We reviewed retrospectively the medical charts of all newborns that had undergone ECT over three years from January 2006 to December 2008. Causes of jaundice, demographic data of the patients, and details of ECT and ECT-related adverse events were recorded. A total of 176 ECT procedures were performed in 150 neonates in the three-year study period. The mean total serum bilirubin before ECT was 29.59 +/- 6.88 mg/dl. Those infants requiring more than one ECT had higher total serum bilirubin than neonates with single ECT, but the difference was not significant (35.66 +/- 12.21 vs. 29.12 +/- 6.30 mg/dl, p = 0.09). The most common cause of ECT was ABO incompatibility (49.3%), Rh disease (7.3%) and idiopathic (28%). Among the adverse events related to ECT, thrombocytopenia (36.4%), hypocalcemia (25.5%), apnea (20%), and infection (10.9%) were noted commonly. No case of ECT-related mortality was observed. All of the adverse events resolved completely before discharge. ABO isoimmunization was the most common cause of ECT in this study. The majority of adverse events associated with ECT are asymptomatic and reversible.