In neonates with prenatal alloimmune liver disease, exchange transfusion (ET) and intravenous immunoglobulin (IVIG) are potentially life-saving therapeutic options (GALD). Early ET has been the standard of treatment in our institution for symptomatic newborns with suspected GALD since 2008. The purpose of this study was to look at the outcomes of this technique. All neonates who underwent ET for suspected GALD were identified and their clinical course and outcomes were evaluated in a descriptive cohort study from 2008 to 2018. In survivors, liver function parameters before ET were compared to maximal levels after ET and after discharge. During the 11-year period, 12 babies with suspected GALD got ET at a median chronological age of 11 days and gestational age of 38 weeks. Survival without a liver transplant was 10 of 12 in the general cohort and 7 of 9 among those who met the criteria for acute liver failure. Two patients died, one after a liver transplant. Even among survivors, direct bilirubin levels generally rose following ET. After an 8-month follow-up, all survivors healed and were discharged from the pediatric hepatology outpatient clinic. A modest diagnostic work-up followed by early ET in infants with suspected GALD may result in good results. More information is needed to create an evidence-based clinical approach to GALD.