<p>Cerebral stroke is a significant cause of death and disability. Ischemic stroke, comprising 85% of cases, can be treated with intravenous recombinant tissue plasminogen activator (IV-rTPA) within 4.5 h or endovascular thrombectomy (EVT) within 24 h in appropriately selected patients. IV-rTPA is often ineffective for large vessel occlusions, and EVT is not universally available, leading to conservative treatment. This study aimed to investigate the effects of Edaravone on the clinical and radiological recovery of patients with ischemic stroke, large vessel occlusion, who did not receive IV-rTPA and EVT. To the best of our knowledge, this study is the first to be conducted in this patient population and is a prelude to further studies. A double-blinded clinical trial enrolled 60 ischemic stroke patients (NIHSS &gt; 16) within 24 h of onset who were ineligible for IV-rTPA or EVT. Patients were randomized to Edaravone group (<i>n</i> = 30) and non-Edaravone group (<i>n</i> = 30). Clinical evaluation used NIHSS score, and radiological assessment used ASPECT score. Demographic data showed no significant differences between groups in age (<i>p</i> = 0.744), gender (<i>p</i> = 0.782), or BMI (<i>p</i> = 0.658). Hospitalization duration was also similar (<i>p</i> = 0.508). Comorbidities were common (90%) with no significant intergroup differences (p ≥ 0.05). The Edaravone group showed significant improvement in ASPECT score post-intervention (<i>p</i> = 0.012). NIHSS scores did not differ significantly (<i>p</i> = 0.312). Edaravone improved radiological outcomes but not clinical outcomes in ischemic stroke patients with NIHSS scores &gt; 16 who did not receive IV-rTPA and EVT. Further investigation into Edaravone's effectiveness is warranted, particularly in patients with lower NIHSS scores, as well as longer follow-up periods.</p>