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Background Patients with moderate-to-severe pre-stroke disability (PSD; modified Rankin Scale [mRS] 3-5) are frequently excluded from endovascular thrombectomy (EVT) despite representing a substantial proportion of patients with large-vessel occlusion (LVO). Data to guide EVT use in this population remains limited. This study evaluated functional outcomes after EVT in patients with PSD, including the impact of successful reperfusion and a comparison with non-disabled patients.Methods We analyzed consecutive EVT-treated LVO patients with pre-stroke mRS 3-5 from the international Stroke Thrombectomy and Aneurysm Registry (STAR) between January 2016 and May 2025. The primary outcome was utility-weighted mRS (UW-mRS) at discharge and 90 days. Outcomes were compared between patients achieving successful (mTICI 2b-3) and unsuccessful (mTICI 0-2a) reperfusion using propensity score matching (3:1). Multivariable logistic regression identified independent predictors of disability worsening. Functional outcomes were additionally compared between propensity score-matched patients with baseline mRS 3-4 and mRS 0-1.Results Among 8,289 EVT-treated patients, 781 had PSD (median age 79 years; 58% women). After matching, 344 patients with successful reperfusion were compared to 123 with unsuccessful reperfusion. Successful reperfusion was associated with lower rates of functional worsening (62.2% vs 79.6%; OR 0.40, 95% CI 0.25-0.70; p<.001), higher likelihood of improvement from baseline (17.8% vs 5.7%; OR 3.6, 95% CI 1.55-8.2; p<.001), and lower 90-day mortality (39.8% vs 57.7%; OR 0.40, 95% CI 0.30-0.80; p<.001). Intraprocedural complications were less frequent with successful reperfusion (7.4% vs 17.7%; p<.001), while sICH rates were similar (6.3% vs. 5.3%; p>.9). In multivariable analysis, (OR 1.03 per year; p<.001), higher admission NIHSS (OR 1.06 per point; p<0.001), and longer procedure time (OR 1.006 per minute; p<.05) independently predicted functional worsening. Compared with matched patients with mRS 0-1 (n=2,126), those with mRS 3-4 had smaller increases in disability from baseline (0.7 vs. 0.3, p<.001), but worse absolute functional outcomes and higher mortality at 90 days (45.2% vs 31.7%; OR 1.71, 95% CI 1.42-2.06; p<.001).Conclusion Among patients with moderate-to-severe PSD undergoing EVT, successful reperfusion is associated with reduced functional worsening, increased likelihood of improvement, and lower mortality without increased hemorrhagic risk. Although absolute outcomes remain poorer than in patients without baseline disability, the relative functional benefit suggests that EVT may be a reasonable option in carefully selected patients with PSD.Disclosures A. Tfaily: None. T. Ma: None. A. Rai: None. S. Wolfe: None. S. Yoshimura: None. I. Maier: None. C. Ogilvy: None. M. Ezzeldin: None. M. Psychogios: None. J. Mascitelli: None. P. Navia: None. V. Inoa: None. L. Elijovich: None. C. Nickele: None. M. Motiwala: None. D. Romano: None. I. Fragata: None. M. Park: None. E. Daglioglu: None. M. Levitt: None. R. Crosa: None. M. Moss: None. J. Dye: None. A. Polifica: None. R. Grandhi: None. M. Mokin: None. B. Howard: None. C. Cawley: None. X. Hu: None. A. Alawieh: 1; C; NIH, Abbott Point of Care, Inc, Department of Defense. J. Grossberg: None.