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Background and Purpose: Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions., Methods: Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University., Results: A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (≤10=0, 11-20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8-10=0, ≤7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75-15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96-17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores., Conclusions: The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.