© 2016 by the American Burn Association. Blood loss during grafting surgery represents a major concern of this procedure and the development of hemostatic agents for this indication is highly desirable. TT-173 is the first biologically active treatment based on tissue factor instead of thrombin. This study sought to investigate the efficacy, systemic absorption, and toxicology of TT-173 in animal models to support clinical evaluation of the product in donor sites of patients subjected to skin grafting. Procoagulant efficacy of 148 μg of TT-173 was evaluated in pigs in presence and absence of anticoagulant treatment with unfractioned heparin. Systemic absorption was quantified and characterized in rats subjected to severe skin lesions with affectation of muscular plane using TT-173 radiolabeled with 125I. The same animal model was used to test the toxicology of a dose of 80 μg of the product. Application of TT-173 significantly reduced the bleeding time of donor sites, even under anticoagulant treatment. Systemic absorption was low; it was excreted through urine and did not concentrate in organs such as liver, lung, or spleen suggesting that the absorbed dose could correspond to degradation fragments without procoagulant activity. Finally, a dose of 80 μg of TT-173 did not cause analytical disturbances suggestive of intravascular coagulation or any other adverse reaction. Nonclinical data obtained suggest that TT-173 could be useful to reduce the blood loss associated to burns treatment and support the clinical evaluation of the product in donor sites of patients subjected to skin grafting.