Objective: Patients with severe traumatic brain injury (TBI) are commonly intubated during prehospital treatment despite a lack of evidence that this is beneficial. Accumulating evidence even suggests that prehospital intubation may be hazardous, in particular when performed by inexperienced EMS clinicians. To expand the limited knowledge base, we studied the relationship between prehospital intubation and hospital mortality in patients with severe TBI in a large Dutch trauma database. We specifically hypothesized that the relationship differs depending on whether a physician-based emergency medical service (EMS) was involved in the treatment, as opposed to intubation by paramedics. Methods: A retrospective analysis was performed using the Dutch Nationwide Trauma Registry that includes all trauma patients in the Netherlands who are admitted to any hospital with an emergency department. All patients treated for severe TBI (Head Abbreviated Injury Scale score ≥4) between January 2015 and December 2019 were selected. Multivariable logistic regression was used to assess the relationship between prehospital intubation and mortality while adjusting for potential confounders. An interaction term between prehospital intubation and the involvement of physician-based EMS was added to the model. Complete case analysis as well as multiple imputation were performed. Results: 8946 patients (62% male, median age 63 years) were analyzed. The hospital mortality was 26.4%. Overall, a relationship between prehospital intubation and higher mortality was observed (complete case: OR 1.86, 95% CI 1.35–2.57, p < 0.001; multiple imputation: OR 1.92, 95% CI 1.56–2.36, p < 0.001). Adding the interaction revealed that the relationship of prehospital intubation may depend on whether physician-based EMS is involved in the treatment (complete case: p = 0.044; multiple imputation: p = 0.062). Physician-based EMS involvement attenuated but did not completely remove the detrimental association between prehospital intubation and mortality. ...