Background Data on outcomes of critically ill patients requiring mechanical ventilation at the onset of stroke are limited. Objective To assess the hospital and long-term functional outcomes of patients with stroke who require mechanical ventilation. Methods This retrospective single-center cohort study performed from 1994 to 2008 involved adult patients within 7 days of stroke onset and who required intensive care unit admission and mechanical ventilation. Results A total of 274 patients requiring mechanical ventilation at the onset of stroke were analyzed. Indications for intubation included coma in 195 patients (71%). The median (interquartile range) score on the Glasgow Coma Scale at admission to the intensive care unit was 6 (3-9). Forty-four patients (16%) had sepsis at intensive care unit admission. The overall hospital mortality rate was 53%. After adjustment for confounders, severity of illness at admission as assessed by the Simplified Acute Physiology Score II (odds ratio, 1.07; 95% CI, 1.05-1.10), anisocoria (odds ratio, 5.26; 95% CI, 1.76-15.80), and sepsis at intensive care unit admission (odds ratio, 0.40; 95% CI, 0.19-0.85) were associated with outcome. At 1 year, median (interquartile range) modified Rankin Scale score was 6 (2-6). Only 89 patients (32%) exhibited mild to moderate neurologic impairment. Conclusion In this study, adult patients requiring mechanical ventilation at the onset of stroke experienced high 1-year mortality, with survivors having poor functional status.