We hypothesized that variation in extubating brain injured patients would affect the incidence of nosocomial pneumonia, length of stay, and hospital charges. In a prospective cohort of consecutive, intubated brain-injured patients, we evaluated daily: intubation status, spontaneous ventilatory parameters, gas exchange, neurologic status, and specific outcomes listed above. Of 136 patients, 99 (73%) were extubated within 48 h of meeting defined readiness criteria. The other 37 patients (27%) remained intubated for a median 3 d (range, 2 to 19). Patients with delayed extubation developed more pneumonias (38 versus 21%, p < 0.05) and had longer intensive care unit (median, 8.6 versus 3.8 d; p < 0.001) and hospital (median, 19.9 versus 13.2 d; p = 0.009) stays. Practice variation existed after stratifying for differences in Glasgow Coma Scale scores (10 versus 7, p < 0.001) at time of meeting readiness criteria, particularly for comatose patients. There was a similar reintubation rate. Median hospital charges were $29,057.00 higher for extubation delay patients (p < 0.001). This study does not support delaying extubating patients when impaired neurologic status is the only concern prolonging intubation. A randomized trial of extubation at the time brain-injured patients fulfill standard weaning criteria is justifiable.