Background The incidence of trauma patients with a positive marijuana screen (pMS) is increasing but the effects of marijuana on outcomes have varied in previous studies. A recent statewide analysis demonstrated decreased mortality for intensive care unit (ICU) trauma patients with pMS. Thus, we hypothesized a pMS to be associated with a decreased risk of mortality for all trauma patients. Methods The 2017 Trauma Quality Improvement Program (TQIP) database was queried for adult (≥18 years-old) pMS patients, who were compared to patients negative for all drugs and alcohol (nDS). Patients not drug tested or testing positive for drug(s)/alcohol other than marijuana were excluded. Multivariable logistic regression was used to evaluate risk of mortality after controlling for known predictors of mortality including age, sex, injury severity, vital signs, and comorbidities. Additional subgroup analyses were performed for ICU patients and younger adults (<40 years-old). Results From 141 737 tested patients, 23 310 (16.4%) had an isolated pMS. Patients with pMS were younger ( P < .001) but had a similar median injury severity score (ISS) (9, P = .42) compared to nDS patients. On multivariable analysis the associated risk of mortality was lower for pMS (OR .79, .71-.87, P < .001) compared to nDS patients. Subgroups analyses also demonstrated decreased associated risk of mortality for ICU and younger patients (both P < .05). Discussion Patients with a pMS had decreased associated risk of mortality compared to nDS patients, including subgroups of ICU and younger patients. These findings require corroboration with future prospective clinical study and basic science evaluation to ascertain the exact pathophysiologic basis and thereby target potential interventions.