This study reports on the results of hemorrhagic shock (HS) plus resuscitation on the coagulation profile in severely injured patients and on the role of fresh frozen plasma (FFP) supplementation in a canine HS model. Primary hemostasis (platelet plug), secondary hemostasis (fibrin clot), and fibrinolysis were assayed in 22 injured patients who received an average of 21 units of packed red blood cells (PRBCs), 16.5 L crystalloid solution, and 1.25 L FFP during operation for control of bleeding. Measurements were obtained during operation and postoperatively at 5, 15, 36, and 84 hours and at 26 days. The platelet count during operation was 113,000/mm3, decreased to a nadir of 76,000/mm3 at 48 hours, and then increased to 563,000/mm2 by convalescence. Platelets were not given with resuscitation. The bleeding times and aggregation studies mirrored platelet levels until convalescence. HS led to significant reductions in fibrinogen (factor I), factor V, and factor VIII that normalized by day 1. The fibrinogen increased to supranormal levels by day 4 through day 26. Clotting times mirrored fibrinogen, factor V, and factor VIII levels. Fibrin split products were normal during operation and increased postoperatively through day 26. The increase in fibrin split products paralleled the increase in fibrinogen. The role of FFP supplementation in HS resuscitation was tested in two separate studies. After HS, the animals were resuscitated with shed blood and crystalloid; half the animals also received FFP. FFP did not improve the coagulation factors, fibrinogen and factors II, V, VII, and VIII. Thus, routine FFP supplementation for HS in humans was abandoned. This led to unexpected postoperative bleeding that in one instance caused death. Therefore, a second controlled study was used in which the FFP was given not only during blood volume restoration but also for an additional hour during continued ongoing controlled hemorrhage without shock. The second study demonstrated that the FFP prevented the reduction in coagulation factors compared with animals not receiving FFP. Clotting times paralleled coagulation protein levels. FFP is now used to supplement HS resuscitation in humans. Resuscitation from hemorrhagic shock can be successfully implemented by restoration of blood loss with blood, crystalloid, and FFP added to maintain coagulation proteins.