Background: Acute ischemic stroke (AIS) is a neurological impairment that lasts for 60 minutes or less and is caused by localized cerebral ischemia. Matrix Metalloproteinase-9(MMP-9) is edema development, activation of proinflammatory cytokines & destruction to the blood-brain barrier are all associated with the pathogenic events that take place during an ischemic stroke and destruction of myelin proteins. Objective: We focused our study on assessing the role of elevated serum MMP-9 and the risk of ischemic stroke in our patients within 24 hours of the stroke's commencement and its connection to the severity of an ischemic stroke. Methods: The Neurology Department's Intensive Care Unit & Stroke Unit at Zagazig University Hospitals conducted this cohort research . The study included 54 patients (31 females and 23 males), presented with a first-time AIS clinical diagnosis. Results: There was a statistically significant inverse relationship between the blood MMP-9 level and the GCS upon admission. There was observed to be a statistically significant positive link between both NIHSS scores and infarction size. The best cutoff of MMP-9 in the prediction of severe stroke was ≥ 1091 ng/ml. Also, the best cutoff of MMP-9 in the prediction of large-size infarction was ≥ 1042. Conclusion: Serum Matrix Metalloproteinase-9 may be a useful predictive indicator for initial risk categorization in individuals experiencing acute ischemic stroke.