The effect of burn wound size on the activation of fibrinolysis, coagulation, and contact factors was analyzed in 60 thermal injury patients. Blood samples from 47 male patients and 13 female patients, (average age 37 years; range 1.5–70 years) were collected within the first 36 hours and at 5–7 days following injury. The patient population was categorized by percentage of burn (second degree and/or third degree): <20%, n = 22; 20%-40%, n = 18; <40%, n = 20. The average percentage of burn was 32% (range, 4%-95%). The mechanism of injury was by flame (25), explosion and flame (19), scald (12), electric (3), or chemicals (1). An associated inhalation injury was present in 12 patients. The overall mortality rate was 13% (8). Sepsis or serious infection occurred in 23% (14) of the patients. On admission, 83% of the patients had normal prothrombin times (PT) and activated partial thromboplastin times (APTT). However, specific hemostatic variables showed marked changes. Admission hemostatic markers that correlated with the severity of injury were: tissue-plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (D-di), plasminogen (Pig), proteins C and S (PrC and PrS), antithrombin III (ATIII), thrombin-antithrombin complex (TAT), kallikrein (Kal:c), kinin (Kin), C1 esterase inhibitor (C1lnh), and factor VII clotting and antigen (FVIkc, FVIhag). These data suggest that during the early course following burn injury, thrombogenicity is increased (TAT↑) because of a decrease in ATIII, PrC, and PrS; and fibrinolysis activation (D-di↓) occurs via an increase in tPA with a p value increase in PAI. C1lnh levels were depressed in all groups and may have contributed in part to post-burn fluid sequestration. This study determined that following thermal injury, there is an activation of thrombotic and fibrinolytic mechanisms and that the severity of these abnormalities increases with the severity of injury. The ATIII abnormalities provided the most significant correlation with the clinical status of the patient (p≤ 0.0001). All hemostatic markers, which had a greater sensitivity than the global markers of coagulation, revealed abnormalities, which resolved in the majority of patients by day 7 when given routine resuscitative treatment unless complications developed.