Background: Stroke is the second most common cause of death worldwide and a frequent cause of adult disability in developed countries. No single outcome measure can describe or predict all dimensions of recovery and disability after acute stroke. Several scales have proven reliability and validity in stroke trials. Objectives: The aim of the work was to evaluate the FOUR score predictability for outcome of patients with acute ischemic stroke in comparison with the NIHSS and the GCS. Methods: 127 adult patients with acute ischemic stroke were enrolled. NIHSS, GCS, and FOUR score were collected at 24 and 72 h. Patients were prospectively followed up for the following outcomes; In-hospital or 30 days mortality and Modified Rankin Scale (mRS) at 3 months. The areas under receiver operating characteristic curve (AUC) were compared between the three scores. Results: Twenty-five (19.7%) patients died, and seventy-two (56.7%) had unfavourable outcome. The NIHSS, the GCS, and the FOUR score were not different in predicting in-hospital mortality (AUC: 0.783, 0.779, 0.975,. The NIHSS, the GCS, and the FOUR score done at 24-h were not different in predicting unfavourable outcome (AUC: 0.893, 0.868, and 0.865, respectively). However, the NIHSS done at 72-h showed significantly higher AUC than the GCS score (0.958 versus 0.931, p = 0.041), and higher than the Four score (0.958 versus 0.909, p = 0.011).