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Background Moderate to severe pre-stroke disability (modified Rankin Scale (mRS) score 3–5) is an exclusion criterion for endovascular thrombectomy (EVT) in acute ischemic stroke (AIS), yet outcomes for this group remain underexplored.Methods Patients who underwent EVT, dichotomized to mRS ≤2 or mRS 3–5, between October 2015 and March 2020 were included from a national stroke registry. Favorable functional outcome was defined as mRS 0–2 for the mRS ≤2 cohort or no worsening of the mRS for the mRS 3-5 cohort at hospital discharge and at 6 months. Other outcomes included in-hospital mortality, symptomatic intracranial hemorrhage (sICH), early neurological deterioration (END), and successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3). The effect of successful recanalization on functional outcome and predictors of favorable functional outcome was assessed in the pre-stroke mRS 3-5 group.Results Among 4353 patients included in the study, 203 (4.6%) had moderate to severe pre-stroke disability. No significant differences were found in favorable functional outcome at discharge (30.5% in mRS 3-5 group vs 33.0% in mRS 0-2 group, adjusted OR 1.21, 95% CI 0.87–1.70, P=0.25) and at 6 months (P=0.97), sICH (P=0.39), END (P=0.72), or successful recanalization (P=0.15). In-hospital mortality was higher in the pre-stroke mRS 3-5 group (P<0.009). Successful recanalization was significantly associated with favorable functional outcomes compared with no recanalization (P=0.008). Admission National Institutes of Health Stroke Scale score, onset to arterial puncture time, EVT technique, and successful recanalization independently predicted functional outcome among patients with pre-stroke mRS 3-5.Conclusion Moderate to severe pre-stroke disability was comparable to pre-stroke mRS 0-2 with respect to favorable functional outcomes after EVT, and may not be a justified exclusion criterion for EVT in AIS. Randomized studies are necessary to optimize decision-making and evaluate the broader impact of EVT in this population.