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Importance: Large vessel disease (LVD) stroke subtype carries the highest risk of early recurrent stroke, reaching up to 30% in the first few days. Predictors of early recurrence have been previously described, but less is known regarding infarct expansion and other causes of neurological worsening. We aim to determine the association between impaired perfusion and neurological decline in patients with LVD subtype.Methods: This is a single center retrospective cohort study of all consecutive patients 18 years or older with LVD admitted with a diagnosis of ischemic stroke within 24 hours from symptom onset (12/1/2016 to 3/31/2017). Patients with 1) evidence of ≥ 50% stenosis of a large intra- or extracranial artery on computerized tomography angiography (CTA); 2) symptoms referable to the territory of the affected artery and NIHSS < 15 and 3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable mismatch volume ≥15 mL, defined as perfusion deficit of Tmax > 6sec volume minus infarct volume similar to neuro-interventional trials. The outcome was recurrent cerebrovascular events (RCVE) at 90 days (adjudicated independently by two vascular neurologists) defined as a decline in neurologic function in the absence of a medical cause, or new infarct or infarct extension in the territory of the affected artery. We estimated the hazard ratio (HR) and 95% confidence interval (CI) for unfavorable perfusion imaging as predictor of RCVE using univariable and multivariable Cox proportional hazards models.Results: Sixty-eight patients met our inclusion criteria (mean age 64.7 years; 61.8% male; 58.8% intracranial LVD). When compared to patients without RCVE, patients with RCVE were more likely to have unfavorable mismatch volume [71.4% vs. 14.8%, p<0.001]. This association persisted after adjusting for sex, dual antiplatelet therapy, initial stroke severity, and intracranial location of LVD (adjusted HR 15.6, 95% CI 3.7-66.7, p<0.001).Conclusion: Perfusion mismatch is associated with RCVE in patients with ischemic stroke due to LVD. Pursuit of more aggressive treatment and management strategies may be warranted in this population.