Abstract Background Legalization of recreational marijuana throughout the United States has been associated with increased emergency department visits involving marijuana and its metabolites, tetrahydrocannabinol (THC) and cannabinoids. We investigated the relationship between marijuana use and outcomes after all levels of traumatic brain injury (TBI) from a large multi-center regional dataset. Methods A retrospective review of de-identified patient data from twenty-six regional hospitals, was performed to identify adult patients with mild, moderate, and severe TBI between January 2012 and December 2018, a toxicology screen, and drug screen results. Included patients were divided into four subgroups: 1) No Drugs, 2) THC, 3) Other drugs (one or more drugs not including THC), and...