Prophylactic mechanical ventilation with PEEP of patients with severe injuries prevents or attenuates the clinical manifestations of ARDS. Also, operative stabilization of all major fractures appears to be beneficial in reducing the incidence of ARDS. Primary external or internal fixation of all unstable long-bone fractures combined with prophylactic ventilation is safe and well tolerated, and allows for optimal nursing of the patient. In a group of 58 severely injured patients, treated accordingly to these principles, late death from remote organ failure due to sepsis—which is the main cause of death in multitrauma patients treated with delayed osteosynthesis or conservative fracture treatment—did not occur. Prophylactic mechanical ventilation with PEEP resulted in a significantly lower incidence of ARDS.