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To describe and compare characteristics, ventilatory practices, and associated outcomes among mechanically ventilated patients with different types of brain injury and between neurologic and nonneurologic patients.Secondary analysis of a prospective, observational, and multicenter study on mechanical ventilation.Three hundred forty-nine intensive care units from 23 countries.We included 552 mechanically ventilated neurologic patients (362 patients with stroke and 190 patients with brain trauma). For comparison we used a control group of 4,030 mixed patients who were ventilated for nonneurologic reasons.None.We collected demographics, ventilatory settings, organ failures, and complications arising during ventilation and outcomes. Multivariate logistic regression analysis was performed with intensive care unit mortality as the dependent variable. At admission, a Glasgow Coma Scale score ≤8 was observed in 68% of the stroke, 77% of the brain trauma, and 29% of the nonneurologic patients. Modes of ventilation and use of a lung-protective strategy within the first week of mechanical ventilation were similar between groups. In comparison with nonneurologic patients, patients with neurologic disease developed fewer complications over the course of mechanical ventilation with the exception of a higher rate of ventilator-associated pneumonia in the brain trauma cohort. Neurologic patients showed higher rates of tracheotomy and longer duration of mechanical ventilation. Mortality in the intensive care unit was significantly (p < .001) higher in patients with stroke (45%) than in brain trauma (29%) and nonneurologic disease (30%). Factors associated with mortality were: stroke (in comparison to brain trauma), Glasgow Coma Scale score on day 1, and severity at admission in the intensive care unit.In our study, one of every five mechanically ventilated patients received this therapy as a result of a neurologic disease. This cohort of patients showed a higher mortality rate than nonneurologic patients despite a lower incidence of extracerebral organ dysfunction.