BACKGROUND:Neonates affected by isoimmune hemolytic disease (HDN) are at risk of developing severe hyperbilirubinemia. Studies show that increasing levels of bilirubin impact neonatal neurodevelopment. To avoid complications associated with exchange transfusion, intravenous immunoglobulin G (IVIG) is used to treat hyperbilirubinemia. We included all infants who received more than two doses of IVIG treatment for isoimmune hemolytic disease. We analyzed the incidence of side effects associated with IVIG treatment and the rate of exchange transfusion. METHODS:A retrospective chart review performed between October 2011–October 2022 at East Carolina University Health identified neonates who received more than two doses IVIG for HDN. Neonates of postmenstrual age greater than 28 days old, receiving less than three doses of IVIG or received IVIG for other indications were excluded. The occurrences of adverse events, demographics and use of other medical therapies were reviewed. RESULTS:Eleven neonates were included in the case series. Most common cause of severe hyperbilirubinemia was attributed to ABO incompatibility. Six patients (54%) received three doses of IVIG, and five patients (45%) received four doses of IVIG with bilirubin levels decreasing below exchange transfusion. No treatment exceeding four doses of IVIG was reported, nor adverse events during treatment. CONCLUSIONS:In this cohort of neonates with HDN, bilirubin levels decreased after treatment with multiple doses of IVIG. Future research on recommendations of optimal total number doses of IVIG to reduce the risk for exchange transfusion.