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.