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Objective: Robust arterial collaterals are associated with successful reperfusion after thrombectomy treatment of acute ischemic stroke due to large vessel occlusion (AIS-LVO). Excellent venous outflow (VO) reflects excellent tissue perfusion and collateral status in patients with AIS-LVO. The goal of this study was to determine whether favorable VO profiles assessed on pretreatment CT angiography (CTA) images correlate with successful vessel reperfusion after thrombectomy in patients with AIS-LVO., Methods: This was a multicenter retrospective cohort study of consecutive patients with AIS-LVO treated by thrombectomy. Baseline CTA was used to assess collateral status (Tan scale) and VO using the Cortical Vein Opacification Score (COVES). Favorable VO was defined as COVES ≥3. Primary outcome was excellent vessel reperfusion status (modified Thrombolysis in Cerebral Infarction 2c/3). Secondary outcome was good functional outcome defined as a score of 0 to 2 on the modified Rankin Scale after 90 days., Results: Five hundred sixty-five patients met the inclusion criteria. Multivariable logistic regression analysis showed that favorable VO (odds ratio [OR] 2.10 [95% confidence interval (CI) 1.39-3.16]; p < 0.001) was associated with excellent vessel reperfusion during thrombectomy, regardless of good CTA collateral status (OR 0.87 [95% CI 0.58-1.34]; p = 0.48). A favorable VO profile (OR 8.9 [95%CI 5.3-14.9]; p < 0.001) and excellent vessel reperfusion status (OR 2.7 [95%CI 1.7-4.4]; p < 0.001) were independently associated with good functional outcome adjusted for age, sex, glucose, tissue plasminogen activator administration, good CTA collateral status, and presentation NIH Stroke Scale score., Conclusion: A favorable VO profile is associated with reperfusion success and good functional outcomes in patients with AIS-LVO treated by endovascular thrombectomy., Classification of Evidence: This study provides Class II evidence that a favorable VO profile is associated with reperfusion success and good functional outcomes in patients with AIS-LVO treated by endovascular thrombectomy., (© 2021 American Academy of Neurology.)