Background: Stroke is a medical emergency disease that affects millions of people worldwide annually. Early nursing interventions provided during the acute stage of ischemic stroke are essential in increasing survival rates and shaping patients' long-term prognosis. Critical care nurses have a crucial role in providing high-quality care for ischemic stroke patients which can improve their clinical outcomes. Hence, they must have ongoing and periodical training programs about ischemic stroke nursing management. Aim: The study aimed to evaluate the effect of implementing the ischemic stroke nursing management protocol on critical care nurses' knowledge and practices. Method: A quasi-experimental design was utilized on 56 critical care nurses who were working in the intensive care units affiliated with a University hospital in Egypt. Data were collected by using one tool: Nurses' Knowledge and Practices Regarding Ischemic Stroke Nursing Management Protocol. Results: Highly statistically significant differences were found in nurses' knowledge and practices pre and post the implementation of the ischemic stroke nursing management protocol (P<0.001). Conclusion: The implementation of the ischemic stroke nursing management protocol can improve nurses' knowledge and practices regarding the care of ischemic stroke patients. Recommendations: Continuous in-service training programs on ischemic stroke management should be organized for critical care nurses to enhance their knowledge and practices, and keep them up-to-date and competent.