Nursing care of the high risk neonates requires critical care nursing, which has created a need for highly skilled personnel trained in the art of neonatal intensive care. The incidences of infection among high risk neonates are more frequent due to their immature immune system. It's considered the most serious complications and represents about 60% of neonatal death in Neonatal Intensive Care Unit (NICU), Tanta university hospital. The aim of this study was to evaluate the effectiveness of educational intervention on nurse's performance to control infection at neonatal intensive care unit, Tanta University Hospital. The sample was consisted of all nurses working in the unit and all high risk neonate who were admitted over a period of 3 months. Two tools were used to collect data. Checklist for nurse's performance and health assessment sheet for high risk neonate. The result shows that, before intervention 70.49% of nurses had unsatisfactory grade, while after intervention two-thirds of them (63.39%) were good and 21.31% of nurses were satisfactory in their performance. This difference was statistically significant (p< 0.05). According to condition on discharge, it was found that 76% of study group improved, compared to 60% of control group. In Conclusion: Risk of infection can be controlled, if the health team and other workers have understood the principles and methods of controlling infection. Nurses at NICU need pre service as wells in-service educational program to refresh their knowledge and improve their skills.