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Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine.Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale).Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%-35.2%) and ranged from 10.8% to 44.2% across centres (χ(2) test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ(2) test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care.Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury. [ABSTRACT FROM AUTHOR]