Background: Meconium Aspiration Syndrome is defined as well as respiratory distress  in  neonates born through meconium stained amniotic fluid whose symptoms cannot be otherwise explained. The nurse role is assessing the signs of distress, keep normal temperature, prevent aspiration, and observe for complications. This study aimed to evaluate the effect of educational guidelines on nurses' performance toward neonates suffering from meconium aspiration syndrome.Design: A quasi- experimental design was used in the current study. Settings: The study was conducted in Neonatal Intensive Care Units at Specialized Pediatric Hospital at Benha City, Egypt.Study subjects: A convenient sample of (62)  nurses and a purposive sample of (62) neonates suffering from meconium aspiration syndrome and need hospitalization. Tools of data collection: Tool (1): A structured interviewing questionnaire sheet consists of Part (1): Personal characteristics of the studied nurses, Part (2): Personal characteristics of the studied neonates and Part (3): Nurses' knowledge regarding meconium aspiration syndrome. Tool (II): An observational checklist to assess nurses' practices. Results: Majority of the studied nurses had good level of total knowledge in post-educational guidelines compared to pre-educational guidelines implementation. Also, the majority of the studied nurses had competent level of total practice in post educational guidelines. Conclusion: The educational guidelines were effective in improving nurses' knowledge and practice regarding care of neonates with meconium aspiration syndrome. There was a positive correlation between nurses' total level of knowledge and practices pre and post educational guidelines implementation. Recommendation: Conducted regular training programs and workshops for nurses regarding care of neonates with meconium aspiration syndrome.