Objective: To determine the major risk factors related to exchange transfusion in pregnancies afflicted with RhD hemolytic disease of the fetus and newborn (HDFN). Methods: A cohort study of 124 infants born with this disease between April 2006 and June 2009 at the Fernandes Figueira Institute. Data on maternal history, prenatal care, delivery and neonatal parameters were subjected to univariate analysis to determine their relationship to severe disease outcome, represented by the need for exchange transfusion. Significant variables were subjected to multivariate and multi level analysis. Results: Diverse simulations were performed in the model to choose the most representative ones. As final result, intrauterine transfusion (RR: 2,54 [1,64-4,00]), jaundice (RR: 2,77 [1,76-4,39]), peak serum bilirubin levels during hospitalization (RR: 1,16 [1,11-1,22]), were the variables found to establish an independent and statistically significant relationship with severe outcome. Conclusion: Recognition of risk factors for exchange transfusion in pregnancies afflicted with RhD HDFN is possible and necessary regarding newborn care following delivery.