Background: Exchange transfusion is emergency procedure for severe neonatal hyperbilirbinemia in the world. This procedure need a medical continued expertise for life-saving intervention and nursing care for preparation pre, during and post procedures Aim: Assess nurses 'performance in caring of neonates undergoing blood exchange transfusion in Neonatal Intensive Care Units. Design: A descriptive design was utilized. Subjects and Setting of the study included forty nurses working in different places namely Elshohada Hospital, University Hospital affiliated to Elmonfia, General Shoubra Hospital and 7 Ahmad Maher Teaching Hospital. Tools: Two tools:1. Predesigned Questionnaire, 2. Observational checklists. Results: the study results revealed that one quarter of the studied nurses had good knowledge regarding exchange transfusion for the neonates. Also, more than two thirds of the studied nurses had competent practices regarding care of neonates undergoing exchange transfusion. There was statistically significant relation between total score level of nurses' knowledge regarding exchange transfusion for the neonates and their total score level of practices. Conclusion: Based on findings of the current study, it can be concluded that minority of studied nurses had good knowledge and more than half of them had competent practices regarding care of neonates undergoing exchange transfusion. Recommendations: Encourage nurses to improve and update their knowledge and practices through attending training programs, conference and workshops about care of neonates undergoing exchange transfusion.