Multiple organ failure (MOF) is considered to be the leading cause of death after severe trauma. Although there is extensive literature on MOF, little is known about the pattern, sequence, and onset of this clinical syndrome. The first goal of this clinical study was to define MOF; the second was to assess the typical onset, sequence, and pattern of MOF; and the third was to define certain risk factors for the development of MOF in 342 multiple trauma patients. Patients with an Injury Severity Score (ISS): > 20 (mean 35.7) were included. Three well established MOF scoring methods were used to give strict definitions of MOF: 11.4% of the total patient population developed MOF, and 88.6% did not. Respiratory failure was most frequent in patients developing MOF (74.4%), and these patients had the highest mortality rate (65.5%) compared to patients with failure of other organ systems (liver, cardiovascular system). Generally, the lung is the first organ to fail after injury (failure after 3.7 +/- 2.8 days). Significant renal failure and the need for dialysis decreased to < 5%; other signs of organ dysfunction (gastric, central nervous system) are difficult to verify. Typical risk factors for the development of MOF after severe trauma are the severity, type, and distribution of injury as well as the indicators of prolonged hemorrhagic shock (elevated lactate levels). The main therapeutic efforts, therefore, should be the effective treatment of traumatic hemorrhagic shock during the initial phase, adequate resuscitation, optimal oxygenation, and early surgical treatment.