Background/Aim: It is controversial whether intravenous recombinant tissue plasminogen activator (IV r-tPA) treatment outcomes in cardioembolic strokes differ from other types of strokes. This study aims to investigate the clinical data of patients with cardioembolic and large-vessel atherosclerosis who received IV r-tPA treatment and compare and discuss the results according to the literature. Methods: The data of the patients who were admitted within the first 4.5 hours following the onset of symptoms, diagnosed with acute ischemic stroke in the Neurology clinic of Kütahya Evliya Çelebi Training and Research Hospital and underwent IV r-tPA were evaluated in this retrospective cohort study. Demographic data, clinical and functional results of patients were compared between the two groups (cardioembolic and large vessel atherosclerosis). Results: Eighty-five patients with ischemic stroke who received IV r-tPA treatment due to cardioembolism and large-vessel atherosclerosis were included in the study. There were 51 patients (60%) in the cardioembolic stroke group and 34 patients (40%) in the large vascular atherosclerotic group. There was no significant difference in terms of functional results between the groups (62.7% vs 44.1%; P=0.09). While symptomatic intracerebral hemorrhage was not detected in the large-vessel atherosclerosis group, it occurred in 3.9% of the cardioembolic stroke group. Conclusion: This study proved that functional and clinical results are similar between cardioembolic and large-vessel atherosclerosis patients who were treated with IV r-tPA treatment. Regardless of the etiology, all suitable patients with acute ischemic stroke should be treated with thrombolytic therapy.