The objective of this study was to determine the role of surgical procedures as secondary inflammatory insults in the development of late multiple organ dysfunction syndrome in patients with multiple trauma and to evaluate both specific and nonspecific indicators of the inflammatory response in their ability to indicate the risk of severely injured patients to develop organ failure after secondary operations. In a prospective study of 106 severely injured patients (ISS 40.6) who underwent secondary operations (> 3 days after trauma), we compared the level of preoperative inflammation with the sequelae of surgical trauma. The interventions included facial reconstructions; osteosynthesis of the pelvic girdle, long bones, and spine; and others. Group 1 consisted of 40 patients (38%) who developed respiratory, renal, or hepatic failure, or combinations thereof, within 2 days after the operation or whose preexisting organ dysfunction worsened by more than 20% from baseline. The remaining 66 patients (62%) with an uneventful recovery formed group 2. The preoperative levels of neutrophil elastase (92.2 vs. 61.3 ng/dL), C-reactive protein (12.4 vs. 7.6 mg/dL), and platelet count (118,000 vs. 236,000/microL) were significantly more abnormal in the patients of group 1. PO2/FiO2 ratio was also somewhat lower in group 1 patients (305.5 vs. 351), whereas other parameters (e.g., blood pressure, heart rate, bilirubin, creatinine, urinary output, lactate, pH, and coagulation) did not allow preoperative differentiation between groups 1 and 2. An increased state of inflammation (neutrophil elastase > 85 ng/mL, C-reactive protein > 11 mg/dL, platelet count < 180,000/microL) predicted postoperative organ failure with an accuracy of 79% (sensitivity, 73%; specificity, 83%). We conclude that secondary operations may act as a second insult and may precipitate late multiple organ dysfunction syndrome if they are performed in patients with multiple trauma while they still have an increased level of posttraumatic inflammation. However, future investigations have to show whether postponing surgery until inflammation has subsided or the use of less invasive surgical techniques will decrease the rate of postoperative organ failure in the trauma patient.