Objectives: Concern has recently been expressed with regard to the physiologic effects of primary intramedullary femoral nailing in seriously injured patients. "Damage control orthopaedics" techniques have been proposed, which comprise principally the use of primary external fixation. The aim of this study was to compare the physiologic effects of external femoral fixation with those of intramedullary stabilization over the first 24 hours after femoral fracture using an established large animal (ovine) trauma model. Methods: Under terminal anesthesia, bilateral high-energy femoral fractures and hypovolemic shock were produced using a pneumatic actuator. Twenty-four sheep were randomized into 4 groups and monitored for 24 hours. Group 1-control, group 2-trauma only, group 3-trauma and external fixation, and group 4-trauma and reamed intramedullary nailing. Outcome measures included the following: pulmonary embolic load (transesophageal echocardiography), metabolic base excess, plasma coagulation markers, and polymorphonuclear cell counts obtained from bronchoalveolar lavage samples. Results: The total embolic load was significantly higher (P <0.001) in the intramedullary nailing group. All trauma groups had a significant increase (P <0.05) in prothrombin times with a fall in antithrombin III and fibrinogen levels. However, the type of fracture stabilization used did not significantly affect any of the other outcome measurements. Conclusions: A higher pulmonary embolic load can be expected during early intramedullary femoral fracture stabilization compared with primary external fixation. However, the degree of stimulation to systemic coagulation and pulmonary inflammation by each type of surgery was comparable.