Summary. Background: Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure. Objectives: The purpose of the present study was to develop a clinically relevant definition of ATC and understand the etiology of this endogenous coagulopathy. Patients/methods: We conducted a retrospective cohort study of trauma patients admitted to five international trauma centers and corroborated our findings in a novel rat model of ATC. Coagulation status on emergency department arrival was correlated with trauma and shock severity, mortality and transfusion requirements. 3646 complete records were available for analysis. Results: Patients arriving with a prothrombin time ratio (PTr) > 1.2 had significantly higher mortality and transfusion requirements than patients with a normal PTr (mortality: 22.7% vs. 7.0%; P < 0.001. Packed red blood cells: 3.5 vs. 1.2 units; P < 0.001. Fresh frozen plasma: 2.1 vs. 0.8 units; P < 0.001). The severity of ATC correlated strongly with the combined degree of injury and shock. The rat model controlled for exogenously induced coagulopathy and mirrored the clinical findings. Significant coagulopathy developed only in animals subjected to both trauma and hemorrhagic shock (PTr: 1.30. APTTr: 1.36; both P < 0.001 compared with sham controls). Conclusions: ATC develops endogenously in response to a combination of tissue damage and shock. It is associated with increased mortality and transfusion requirements in a dose-dependent manner. When defined by standard clotting times, a PTr > 1.2 should be adopted as a clinically relevant definition of ATC.