Background: Medication errors (MEs) are a critical patient safety issue. Nurses are often responsible for administering medication to patients, thus their perceptions and performance regarding medication errors in emergency room can provide valuable guidance for the development of interventions aimed to mitigate errors. Aim: The aim of this study was to assess the nurses' perception and performance regarding medication errors in Emergency room. Design: A descriptive exploratory research design was utilized in this study. Setting: The study was conducted at the Emergency room at El- Fayoum University hospitals. Subjects: The study subjects included a convenient sample of all staff nurses (n=65) in the Emergency room at El- Fayoum University hospital. Data collection tools: 1^st tool. Nurses' questionnaire regarding medication administration errors in emergency room, 2^nd tool. Nurses' performance observational checklist regarding medication errors in emergency room, 3^ed tool. The Modified Gladstone scale (self-administered sheet). Results: the current study revealed 78.5% of the studied nurses have an unsatisfactory level of total knowledge regarding medication errors while 72.3% of the studied nurses have incomplete performance regarding medication errors in emergency room and 53.8% of the studied nurses have negative perception regarding medication errors in emergency room Conclusion: the current study revealed more than three quarters of the studied nurses had unsatisfactory level of total knowledge regarding medication errors in emergency room and slightly less than three quarters had incomplete performance room. Also, more than half of them had a negative perception. Recommendations: Develop training programs for nurses in emergency room to enhance their knowledge and performance regarding medication errors.