Background: A medical-psychiatric unit (MPU) is a special ward where staff is trained in caring for patients with psychiatric or behavioural problems that need hospitalisation for physical health problems. It is well known that these patients are at higher risk of complications and have a longer length of stay resulting in higher costs than patients without psychiatric comorbidity. The objective of this study was to analyse the trauma patient population of the first 10 years of existence of the MPU in a level I trauma center. Patients and methods: A retrospective analysis was performed in 2-year cohorts from 2006 to 2016. All trauma patients admitted to the MPU were compared with the overall trauma patient population in VUmc. Data (psychiatric diagnosis, substance abuse, trauma scores, surgical interventions, complications, mortality) were extracted from individual patient notes and the Regional Trauma Registry. Results: 258 patients were identified. 36% of all patients had a history of previous psychiatric admission and 30% had attempted suicide at least once in their lifetime. Substance abuse was the most common psychiatric diagnosis (39%), with psychotic disorder (28%) in second place. The median hospital stay was 21 days. Median MPU length of stay was 10 days (range 1–160). Injuries were self-inflicted in 57%. The most common mechanism of injury was fall from height with intentional jumping in second place. Penetrating injury rate was 24% and 33% had an ISS ≥ 16, compared to 5% and 15%, respectively, in the overall trauma patient population. The most common injuries were those of the head and neck. Complication rate was 49%. Conclusion: Trauma patients that were admitted to the MPU of an urban level I trauma center had serious psychiatric comorbidity as well as high injury severity. Penetrating injury was much more common than in the overall trauma patient population. A high complication rate was noted. The high psychiatric comorbidity and the complicated care warrants combined psychiatric and somatic (nursing) care for this subpopulation of trauma patients. This should be taken into account in the prehospital triage to a trauma center. The institution of a MPU in level I trauma centers is recommended.