Background: Stroke is a major public health problem worldwide and in Egypt. It is a life-threatening disease that requires early recognition, management and collaboration of all members of the health care team. Critical care nurses play an important role in all phases of care for stroke patients. Aim: study the impact of a designed acute stroke nursing management protocol on critical care nurses’ knowledge and practices. Hypothesis: The mean post-test total knowledge and practices scores of critical care nurses who are exposed to the designed nursing management protocol of care will be higher than their mean pre-test scores. Sample: A convenience sample of (30) nurses. Design: A quasi-experimental, single group interrupted time series design was utilized. Tools: tool (1): Nurses Knowledge Assessment Questionnaire (2): Pre /post observational checklists. Critical care nurses were assessed three times: before implementing the protocol of care, immediately after implementing the protocol of care, and two months after. Results: the current study revealed that most of the studied sample (80%) were female in the middle age groups (X= 30.16, SD =7.71), and the total mean knowledge scores in the second and third assessment times (X= 70.47, SD =6.27, X= 66.67, SD= 8.1) respectively, improved as compared to the first assessment time (X= 24.23, SD= 11.24) with a significant statistical difference between the three assessment times (F= 246.344, P ≤ 0.05). The total mean practices scores in the second assessment and third assessment times (X= 45.90, SD= 5.02, X= 39.87, SD= 4.54) respectively, was higher than the total mean practices scores in the first assessment (X= 22.10, SD= 7.42) with a significant statistical differences between the three assessments (F= 131.913, P ≤ 0.05) . A significant statistical differences between the three assessments was found regarding utilization of NIHSS and GCS (F= 420.310, 123.189, P ≤ 0.05). Conclusion: effectiveness of implementing the protocol of care where nurses’ knowledge and practices improved significantly as compared before implementing the protocol of care. So, the study recommends continuous training and education for nurses to improve their knowledge and practices with availability of Arabic references.