Background: medication safety is a priority for health care organizations worldwide. Nurses need to identify the challenges they face when administering medications to their patients. Aim: To assess nurses' performance regarding safety infusion of look-alike sound-alike medication. Subjects & sitting: Convenient samples of all available nurses (40) were working in intensive care units at Ain   Shams   University Hospitals. Design: A descriptive research design Tools: 1. Medication Safety Assessment Questionnaire. 2. Intravenous infusion of look-alike sound-alike medications observational checklist.   Results:   By testing the relation between total knowledge regarding look-alike sound-alike medications and total practice, there was highly statistically significance difference between total knowledge and total practice Conclusion:   The study subjects had performance deficit regarding safety infusion of look-alike sound-alike medications, which were affected by the following; the total nurses' knowledge regarding administration of look-alike sound-alike medications was unsatisfactory. This can be explained by the highly statistically significance relation between total practice and total knowledge. Recommendations: Continuous intravenous infusions of look-alike sound-alike medication educational programs until nurses reach the purpose of competency.