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Background Despite successful reperfusion following endovascular thrombectomy (EVT), a substantial proportion of patients with acute large vessel occlusion stroke (LVOS) fail to achieve favorable functional outcomes. We evaluated the association between clinical and imaging metrics and futile reperfusion.Methods We conducted a retrospective analysis of a prospectively maintained stroke database from January 2020 to August 2024. Patients with anterior circulation LVOS who received intravenous thrombolysis within 4.5 hours of last-known-well followed by mechanical thrombectomy and achieved successful reperfusion (final eTICI 2b/2c/3) with available 90-day modified Rankin Scale (mRS) outcomes were included. Futile reperfusion was defined as poor functional outcome (mRS 3-6) despite successful reperfusion. Baseline clinical, imaging, and workflow variables were compared between beneficial (mRS 0-2) and futile reperfusion, and multivariable logistic regression was performed to identify independent predictors of futile reperfusion.Results Among 5,366 stroke alerts, 256 patients met inclusion criteria for the final eTICI 2b/2c/3 cohort with thrombectomy performed and available 90-day mRS outcome data. Beneficial reperfusion occurred in 146 patients (57.0%), whereas 110 patients (43.0%) had futile reperfusion. Patients with futile reperfusion were older (median 74 vs 69 years, p=0.001), had higher admission glucose (131.0 vs 120.5 mg/dL, p=0.005), and greater baseline stroke severity (NIHSS 19 vs 15, p<0.001). Favorable collateral circulation (Tan score ≥2) was less common among patients with futile reperfusion (59.4% vs 84.3%, p<0.001). In the final multivariable model, increasing age (aOR 1.04, 95% CI 1.01-1.07), higher baseline serum glucose (aOR 1.01, 95% CI 1.00-1.01), higher baseline NIHSS (aOR 1.10, 95% CI 1.04-1.16), longer door-to-groin time (aOR 1.01, 95% CI 1.00-1.01), a history of hypertension (aOR 2.49, 95% CI 1.12-5.51), and a greater number of thrombectomy passes (aOR 1.23, 95% CI 1.00-1.50) were independently associated with futile reperfusion, whereas pre-stroke functional independence and favorable collaterals were associated with lower odds of futile reperfusion.Conclusions Futile reperfusion occurred in approximately 43% of patients despite successful endovascular therapy. Independent predictors included nonmodifiable factors such as older age, higher baseline NIHSS, and poor collateral status, as well as modifiable factors including admission hyperglycemia and longer door-to-groin times. These findings suggest that targeting early hyperglycemia management and reducing workflow delays may help improve outcomes following succesful angiographic reperfusion.Disclosures K. Darko: None. M. Cao: None. G. James: None. J. Kocherzat: None. S. Kozloski: None. C. Neal: None. C. Schirmer: None.