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Background: Upon hospital arrival, patients with mild or rapidly improving acute ischemic strokes (AIS) are frequently not treated with IV-tPA. Recent guidelines from the American Heart Association report that diagnosis on imaging of large vessel occlusion (LVO) despite mild stroke severity leads to increased risk of poorer outcomes. The objective of our study was to examine outcomes following tPA in this AIS population.Methods: The study included all AIS patients with an admission NIHSS ≤7 and diagnosis of a LVO on imaging from a single comprehensive stroke center between 2010-2016. Patients were excluded due to missing contraindications to tPA or with a symptom to arrival time of >4.5 hours (n=234). We compared patients who received tPA to those who received no treatment because of mild or rapidly improving symptoms. Outcomes were sICH, improvement in NIHSS score, discharge mRS ≤2, and in-hospital mortality. Patient characteristics were compared univariately, and step-wise logistic regression was used to adjust for confounding variables. Entry criterion was P=0.2 and exit criterion was P=0.07.Results: There were 76 patients with an AIS diagnosis of LVO. Of these patients, 39 (51%) were treated with tPA and 37 (49%) were not treated. Overall, the median (IQR) age was 72 (61-82.5). Patients treated with tPA had a median admission NIHSS of 5 (3-6), and a larger proportion were male (77%) and smokers (4%). Patients without tPA treatment had a median NIHSS of 2 (1-3), and a larger proportion had hypertension (49%). All outcomes were not significantly different between groups after adjustment (Table 1). There were no patients with sICH.Conclusions: Our study suggests that tPA in mild LVO patients does not introduce additional risk in terms of sICH, in-hospital mortality, change in NIHSS, or discharge mRS. Further justification for withholding tPA in this group should be based on 90-day mRS scores, in order to better understand long-term functional outcomes.