BACKGROUND: There are multiple approaches to the blood product and fluid resuscitation of a bleeding trauma patient. An in silico model of different trauma resuscitation strategies was constructed to predict their effects on the volumes of the different body fluid compartments and on several important hemostatic factors. STUDY DESIGN AND METHODS: This multicompartment dynamic deterministic model comprised four interconnected modules (hemostatic, resuscitation, body fluid compartment, and dilutional coagulopathy). The model was divided into five resuscitation phases with simulations using six different resuscitation strategies: whole blood (WB) only, conventional component therapy (CCT) only or 10 units of WB followed by CCT, with either 1 L of crystalloid or 1.5 units of WB or red blood cells in the prehospital phase. RESULTS: At the end of the simulations using 1 L of crystalloid fluids in the prehospital resuscitation phase, the use of WB led to a 1.4 g/dL higher hemoglobin concentration, 32 mg/dL higher fibrinogen concentration, and 0.9 L lower total extracellular fluid volume compared to CCT. Prehospital blood product transfusion in place of crystalloid resulted in higher hemoglobin and fibrinogen concentrations and a lower international normalized ratio throughout the resuscitation regardless of the resuscitation strategy used. Throughout both the prehospital crystalloid and prehospital blood product transfusion simulations, the hemoglobin and fibrinogen concentrations and platelet counts were higher, and the international normalized ratio was lower, when WB was used compared to CCT. CONCLUSIONS: This model predicted improved hemostatic factor levels and a smaller total extracellular fluid volume volume when WB was transfused instead of CCT to bleeding trauma patients.