Objective: To explore the association of baseline venous outflow from the occluded cerebral territory and futile recanalization (FR) in patients with acute ischemic stroke due to large vessel occlusion (LVO) in the anterior circulation. Methods: Consecutive patients from a prospectively maintained stroke database were included in this study if they presented with a multimodal CT-confirmed LVO in the anterior circulation and underwent thrombectomy within 24 hours after stroke onset. Excellent recanalization of the occluded artery, defined as final mTICI 2c-3 on digital subtraction angiography, was considered to be futile if patients fail to achieve functional independence (modified Rankin Scale of 0-2) at 90 days. Baseline venous outflow profile was determined by a 7-point semi-quantitative scoring system which assessed ipsilateral venous opacification of the vein of Labbe, Trolard and superficial middle cerebral vein on single-phase CTA source images. Hypoperfusion intensity ratio (HIR, defined as delay time >6 seconds/delay time >3 seconds) was applied to evaluate tissue-level collateral status. Results: 145 patients met the inclusion criteria. Multivariable logistic regression analysis showed that malignant venous outflow (OR 4.30 [95% CI 1.41-14.57]; p =0.013) was independently associated with functional dependence regardless of age, glucose, HIR, early neurologic deterioration, hemorrhagic transformation and final infarct volume. FR was observed in 24/52 (46%) recanalized patients. Stepwise logistic regression revealed a poor venous outflow profile at presentation as an independent predictor of FR (OR 7.04 [95% CI 1.29-50.16]; p =0.03) adjusted for baseline NIH Stroke Scale score, HIR and presence of hemorrhagic transformation. Conclusion: A malignant venous outflow profile at baseline is associated with FR in patients with LVO. The mechanism by which poor venous outflow from the occluded territory hinders clinical recovery despite prompt successful thrombectomy remains to be determined.