Introduction: Exchange transfusion (ET) is an effective mode of therapy in the treatment of hyperbilirubinemia, but is associated with some COMPLICATIONs in 5-10% of the patients, especially in preterm newborns. The most important COMPLICATIONs following exchange transfusion are: Acidosis, thrombocytopenia, hypocalcemia, hyponatremia, hypoglycemia and transmitting infectious agents. This study aims to determine some COMPLICATIONs of exchange transfusion in neonatal hyperbilirueinemia in NICU of 22 Bahman 22nd Hospital in order to promote its safety and efficacy.Materials and Methods: In this study neonates with undergone exchange transfusion due to hyperbilirubinemia were evaluated over a period of 36 months in NICU of 22 Bahman 22nd Hospital from July 2005 to July 2008 in Mashhad. The questionnaires were completed according to the by patients’ data. The data were then and analyzed for statistical results.Results : Of the 28 neonates who entered the study, 3 required more than one ET. COMPLICATION of ET occurred in 24 neonates (85.7%).The most common COMPLICATIONs were being metabolic acidosis (67.9%) and thrombocytopenia (50%).Conclusion: In order to avoid COMPLICATIONs following exchange transfusion, it should be emphasized to have laboratory tests done. For instance, tests of platelet count and arterial blood gases are needed so that in cases of COMPLICATIONs, the available information can facilitate the treatment. They can be treated on time.