IntroductionTraumatic brain injury (TBI) is a leading cause of death and disability, often resulting in prolonged coma and disordered consciousness. There are currently gaps in understanding the factors affecting rehabilitation location and outcome after TBI.ObjectiveTo identify the impact of demographics, comorbidities, and complications on discharge disposition in adults with prolonged coma following TBI.DesignRetrospective cohort study.SettingTertiary care hospitals and trauma centers in the United States.ParticipantsPatients 18 years of age or older with TBI and prolonged coma during the years 2008 to 2015.InterventionNot applicable.Main Outcome MeasuresDemographics, clinical injury data, comorbidities, and complications were collected, and odds ratios (ORs) and descriptive analysis were calculated for mortality, long‐term rehabilitation, and home discharge without services.ResultsA total of 6929 patients with TBI and prolonged coma were included in the final analysis; 3318 (47.9%) were discharged to rehabilitation facilities, 1859 (26.8%) died, and 1752 (25.3%) were discharged home. Older patients and those with higher injury severity scores had significantly higher ORs for mortality and rehab discharge. A total of 58.3% of patients presented with at least one comorbidity. Non‐White ethnicities and self‐pay/uninsured patients were significantly less likely to be discharged to a rehab facility. Furthermore, comorbidities including congestive heart failure (CHF) and diabetes were associated with a significantly increased OR for mortality and rehab discharge compared to home discharge without services.ConclusionsComorbidities, age, and injury severity were the most significant risk factors for increased mortality and acute rehab discharge. Maximizing the treatment of comorbidities including CHF and diabetes has the potential to decrease mortality and adverse outcomes following TBI with prolonged coma.