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Background: Anterior circulation large vessel occlusion (ACLVO) stroke, one of the most devastating stroke subtypes, is associated with substantial economic burden. Identifying predictors of increased ACLVO stroke hospitalization cost is essential to developing cost-effective treatment strategies.Methods: We utilized comprehensive patient-level cost-tracking software to calculate hospitalization costs for ACLVO stroke patients at our institution between July 2012-October 2014. Patient demographics and neuroimaging findings were analyzed. Predictors of hospitalization cost were determined using multivariable linear regression. In addition to our primary analysis (all eligible ACLVO patients), we conducted subgroup analyses by treatment (endovascular, IV tPA-only, and no reperfusion therapy) and sensitivity analyses.Results: 341 patients (median age 69 [IQR 57-80], median NIHSS 16 [IQR 13-21], median hospitalization cost $16,446 [IQR $9823-$27,165]) were included in our primary analysis; final infarct volume (FIV), parenchymal hematoma, age, obstructive sleep apnea, and baseline NIHSS were significant predictors of hospitalization cost (Figure). FIV alone accounted for 20.51% of the total variance in hospitalization cost. Notably, FIV was consistently the most robust predictor of increased cost across primary, subgroup, and sensitivity analyses. Over the observed range of FIVs in our cohort, each additional 1cc of infarcted brain tissue increased hospitalization cost by $122.35.Conclusion: FIV is a critical determinant of increased hospitalization cost in ACLVO stroke. Therapies resulting in reduced FIV may not only improve clinical outcomes, but prove cost-effective.