Damage Control techniques involve primary external fracture fixation to reduce the ‘second hit’ of surgery. This study used a large animal (ovine) trauma model to compare pathophysiological responses of primary external femoral fixation and intramedullary stabilisation. Under terminal anaesthesia bilateral femoral fractures and hypovolaemia were produced using a pneumatic ram. 24 sheep were randomised into 4 groups and monitored for 24 hours. Group 1 – Control; Group 2 – Trauma only; Group 3 – Trauma and external fixation; Group 4 – Trauma and reamed intramedullary stabilisation. Outcome measures: pulmonary embolic load (transoesophageal echocardiography); plasma coagulation markers; bronchoalveolar lavage differential cell counts (neutrophils, lymphocytes and macrophages). Total embolic load was significantly higher (p<0.001) in the intramedullary fixation group (median score 42 versus 20). All trauma groups had a significant increase (p < 0.05) in prothrombin time with a fall in antithrombin III and fibrinogen levels. No significant differences occurred between trauma groups with any coagulation or alveolar lavage marker. Intramedullary femoral fracture fixation produced a relatively higher pulmonary embolic load. However, the initial fracture fixation method did not affect any of the changes seen in the measured coagulation or inflammatory markers during the first 24 hours of injury.