ObjectivesRoad traffic injuries (RTIs) are an important public health problem, especially in low- and middle-income countries (LMICs), and are highly preventable with evidence-based interventions. This study aimed to describe the sociodemographic characteristics, risk factors, and patterns of injury that are associated with in-hospital mortality among patients with RTIs.MethodsA prospective observational study was conducted at 8 hospitals in Cambodia, Ethiopia, Mexico, and Zambia with adult patients who sustained moderate to severe RTIs and were admitted to participating hospitals for at least 24 h. Bivariate and multivariable logistic regression models were used to examine the association between relevant variables and death in-hospital.ResultsThe majority of RTI deaths occurred among males aged 18 to 44 who were pedestrians or riders of 2- or 3-wheeled vehicles. The following variables were associated with in-hospital mortality: Riding a 2- or 3-wheeler (adjusted odds ratio [AOR] 3.30, 95% confidence interval [CI] 1.06-10.23), moderate-severe Glasgow Coma Scale (GCS; AOR 10.27, 95% CI 4.72-22.33), and low systolic blood pressure (AOR 5.97, 95% CI 1.97-18.04).ConclusionsThe findings reinforce the important role of traumatic brain injury (TBI) in RTI deaths and highlight the need for capacity building to develop local neurosurgery expertise to manage and treat TBI in LMICs. Evidence-based prevention strategies such as lowering speed limits in urban areas, protecting users via dedicated footpaths and cycle paths, and increasing helmet use are recommended to mitigate the impact of RTIs and reduce mortality among vulnerable road users. In addition, triage systems should be in place to identify patients with moderate-severe GCS and low systolic blood pressure for immediate and intensive care.