Objective Nearly 7% of the adult US population has symptomatic Attention Deficit Hyperactivity Disorder (ADHD), which is associated with an increased risk for traumatic injury. There is limited data on the outcome of hospitalized trauma patients with ADHD. This study aimed to use a large nationwide database to investigate the relationship between a diagnosis of ADHD and clinical outcomes in hospitalized patients after major trauma. Methods All patients 18 years or older in the National Trauma Database were retrospectively reviewed. Propensity score analysis was used to match patients with and without the diagnosis of ADHD at a 1:1 ratio based on age, sex, race, highest AIS in each region, comorbidities, and the presence of advanced directives limiting care. Outcomes of patients with ADHD admitted to the trauma service between the years 2015 and 2017 were compared to those without ADHD. The primary outcome of interest was in-hospital mortality, while the secondary outcomes included complications and hospital length of stay. Results There were 9399 patients included in the study with a diagnosis of ADHD. These patients were overall more likely to be younger, male, and Caucasian, compared to their matched counterparts without ADHD. ADHD was associated with a significantly lower in-hospital mortality than patients without ADHD. There was no difference in the ICU admission rate, ICU LOS, ventilator use, or complication rates between patients with and without ADHD. Conclusion A diagnosis of ADHD has a complex association with clinical outcomes after trauma. The current large national analysis found that patients with a diagnosis of ADHD had significantly lower overall in-hospital mortality.