Background: Medication safety is a major concern and global issue related to the quality and safety of pediatric patient care. Majority of these errors are preventable if doctors and nurses consult the drug formulary more often, doses and related issues are routinely cross checked during the clinical rounds This study aimed to assess performance of nurses regarding high alert medications in critical care units. Subject and methods: A descriptive design was used to conduct this study. Setting: The study was conducted at critical care units in children Hospital affiliated to Ain Shams University Sample: A convenient sample of 100 nurses was working at the previously mentioned settings. Tools of the study: 1- Predesigned Questionnaire Format to assess characteristic of studied nurses and their knowledge about high alert medications in critical care units. 2- Observational checklist to assess the practice of nurses regarding high alert medications in critical care units. Results: There was a high statistically significant difference between nurses' knowledge level and their practice level regarding high alert medications, with a positive correlation between them. Conclusion: Based on result of the current study, it can be concluded that, critical care nurses have inadequate knowledge and practice regarding selected high alert medications. Nurses with higher educational level had better knowledge and practice score than nurses with low educational level. Recommendations: Based on findings of the current study, implement educational programs and upgrading courses aimed with evidence based guidelines based on nurses' needs to improve their knowledge and practice related to administration of high alert medications.