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We aimed to investigate stroke etiology in our cohort of patients with mild ischemic stroke (MIS) and to study the effect of stroke etiology on patient outcome. We also studied the effect of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in this cohort. We analyzed patients with MIS who were eligible for IV rt-PA presenting within 3 hours of symptom onset with a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5 admitted from March 2006 through June 2009. Stroke etiology was determined using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Primary outcome was the discharge NIHSS score. We identified 110 patients with MIS with a male-to-female ratio of: 1.4:1 and a mean age of 69 ± 13 years. The mean admission NIHSS score was 2 ± 3. The stroke risk factors were identified as: hypertension, 82 patients (75%); previous stroke/transient ischemic attack, 36 patients (33%); and atrial fibrillation, 28 patients (26%). Stroke etiology was identified as: large vessel atherosclerosis (31 patients, 28%), cardioembolism (29, 26%), small vessel occlusion (seven, 6%) and those with other or undetermined conditions (43, 39%). IV rt-PA was administered to 25 patients (23%). Despite the use of IV rt-PA in only one patient with small vessel occlusion, patients in our study with this stroke etiology tended to have better outcomes compared to those with other stroke subtypes, although the difference was not statistically significant. The discharge NIHSS score did not show any statistically significant difference between the treated and untreated patients with MIS. Our study shows that MIS may be caused by non small vessel occlusion in more patients than previously reported and this subgroup of patients with MIS should not be excluded from trials of intravenous and endovascular therapies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)