Antithrombin (AT) is an important endogenous anticoagulant and exhibits marked anti-inflammatory properties. To evaluate the incidence of AT deficiency in severe burn and its correlation to the variables of the abbreviated burn severity index (ABSI), length of hospital stay (LOS) and mortality we collected data on the substitution of human plasma-derived AT concentrate in 201 consecutive patients suffering from severe burn. One hundred and eight patients (54%) developed AT deficiency during their hospitalisation and, according to our institutional practice, received substitution therapy by continuous infusion to maintain physiological plasma activity (70-120%). The mean administered dose served as a measure of AT deficiency. The percentage of patients in an AT deficient state was highest within the first 5 days after injury. It was 26% on day 1 and between 38% and 41% on days 2-5 and thereafter decreased constantly over time. A multiple regression analysis between the dependent variable mean administered dose of AT concentrate and the independent variables age, total body surface area burned (TBSA), gender, inhalation injury (INHAL), full thickness burn (FTB), LOS and mortality was performed. Age, gender and FTB showed no significant influence on the development of AT deficiency. Increasing TBSA and INHAL clearly increase the risk of developing AT deficiency (p-values 0.0001 and 0.037). The analysis also identified AT deficiency as an independent predictor of LOS and mortality (p-values 0.036 and 0.003). Development of AT deficiency is a frequent event after burn with significant correlation to TBSA and INHAL, increased mortality rates and longer hospital stays.