BACKGROUND: To investigate the rates, predictors, and outcomes of prolonged mechanical ventilation (≥ 96 h) following endovascular treatment (EVT) of ischemic stroke. METHODS: Hospitalizations with acute ischemic stroke and EVT were identified using validated codes in the National Inpatient Sample (2010-2015). The primary outcome was prolonged mechanical ventilation defined as ventilation ≥ 96 consecutive hours. We compared hospitalizations involving prolonged ventilation following EVT with those that did not involve prolonged ventilation. Propensity score matching was used to adjust for differences between groups. Clinical predictors of prolonged ventilation were assessed using multivariable conditional logistic regression analyses. RESULTS: Among the 34,184 hospitalizations with EVT, 5087 (14.9%) required prolonged mechanical ventilation. There was a decline in overall intubation and prolonged ventilation during the study period. On multivariable analysis, history of heart failure [OR 1.28 (95% CI 1.05-1.57)] and diabetes [OR 1.22 (95% CI 1-1.50)] was independent predictors of prolonged ventilation following EVT. In a sensitivity analysis of anterior circulation stroke only, heart failure [OR 1.3 (95% CI 1.10-1.61)], diabetes [OR 1.25 (95% CI 1.01-1.57)], and chronic lung disease [OR 1.31 (95% CI 1.03-1.66)] were independent predictors of prolonged ventilation. The weighted proportions of in-hospital mortality, post-procedural shock, acute renal failure, and intracerebral hemorrhage were higher in the prolonged ventilation group. CONCLUSIONS: Among a nationally representative sample of hospitalizations, nearly one-in-six patients had prolonged mechanical ventilation after EVT. Heart failure and diabetes were significantly associated with prolonged mechanical ventilation following EVT. Prolonged ventilation was associated with significant increase in in-hospital mortality and morbidity.