Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicenter retrospective study. This study included 519 adult trauma patients with an injury severity score ≥16. Patients with ≥10 units of red cell concentrate transfusion and/or death during the first 24h were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D-dimer values to be 190mg/dL and 38mg/L, respectively. On the basis of these values, patients were divided into four groups: low D-dimer (<38mg/L)/high fibrinogen (>190mg/dL), low D-dimer (<38mg/L)/low fibrinogen (≤190mg/dL), high D-dimer (≥38mg/L)/high fibrinogen (>190mg/dL), and high D-dimer (≥38mg/L)/low fibrinogen (≤190mg/dL). The survival rate was lower in the high D-dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels.