Purpose <p>We sought to describe the clinical features and outcomes of adult patients with traumatic brain injury in Ontario.</p> Methods <p>We carried out a cohort study of adult patients admitted to an intensive care unit (April 2009 to March 2021) with a first episode of traumatic brain injury. To compare the long-term outcome trajectory after traumatic brain injury, we matched patients with traumatic brain injury 1:1 to patients who survived an intensive care unit admission with multisystem trauma but without traumatic brain injury. We measured in-hospital and long-term all-cause mortality; additional endpoints included 1) new psychiatric diagnosis, 2) epilepsy, 3) venous thromboembolic disease, and 4) sepsis. We estimated hazard ratios (HR) with 95% confidence intervals (CI).</p> Results <p>Overall, we included 13,283 adult patients with traumatic brain injury. The mean age was 54 yr; 72% of patients were male. The most common pre-existing comorbidities were hypertension (39%) and cardiovascular disease (19%). Median follow-up was 5 years; 17% of patients with traumatic brain injury died during their initial hospital stay, and 16% died during long-term follow-up. Sepsis after hospital discharge occurred in 14% of patients; additional outcomes included new psychiatric diagnosis (7%), epilepsy (4%), and venous thromboembolic disease (2%). Surviving traumatic brain injury was associated with a higher hazard of epilepsy (HR, 2.42; 95% CI, 1.99 to 2.95); the risk of other outcomes was similar or lower when compared with survivors without traumatic brain injury.</p> Conclusions <p>Patients with traumatic brain injury have a high risk of in-hospital death. Those who survive the initial hospitalization are at risk of long-term outcomes including new epilepsy.</p>