Background It is important to study the factors affecting the clinical mortality of the severe multiple trauma population. The present study was aimed to identify the potential risk factors that could affect mortality rate of acute lung injury (ALI) in severely injured multiple trauma population and to investigate the effects of certain risk factors on the prognosis of different patient subpopulations.Methods This is a follow-up study treating trauma as a single cause for emergency department (ED) and emergency intensive care unit (EICU) admissions. Patients identified with severe multiple trauma with early onset of ALI were enrolled from five trauma centers. Nineteen potential risk factors affecting the prognosis of ALI were examined by univariate and multivariate Logistic regression analyses to identify the ones that affected the mortality of these severe multiple trauma patients.Results There were 687 multiple trauma patients with post-traumatic ALl admitted to ED and EICU during the study period. The six risk factors that affected the mortality with unadjusted odd ratios (ORs) and 95% confidence intervals (Cls)were Acute Physiology Score and Chronic Health Evaluation Score (APACHE) II score, Injury Severity Score (ISS), duration of trauma, age, aspiration of gastric contents, and disseminated intravascular coagulation (DIC). Specific risk factors also affected different patient subpopulations at different degrees (surviving beyond 24 hours, 72 hours, 28 days and with multiple blood transfusions and higher injury scores).Conclusions Factors of APACHE Ⅱ score, ISS and aspiration of gastric contents that could predict the mortality of ALI may exist in the early stage of trauma. Duration of trauma and DIC that greatly affected and predicted the short- and long-term development and mortality of ALI deserve special attention. Elderly patients (aged beyond 65 years) were the independent risk factor for the secondary sepsis and deterioration of pulmonary function. Patients with these risk factors need aggressive supportive care as early as possible in order to prevent further aggravation.