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Background Multiply injured patients (MIPs) are at risk to develop multiple-organ failure (MOF) and prolonged systemic inflammation response syndrome (SIRS). It is difficult to predict which MIPs are at the highest risk to develop these complications. We have developed a novel method that quantifies the distribution and physical magnitude of all injuries identified on admission computed tomography scanning called the Tissue Damage Volume (TDV) score. We explored how individualized TDV scores corresponded to MOF and SIRS. Materials and methods A retrospective study on 74 MIPs measured mechanical TDV by calculating injury volumes on admission computed tomography scans of all injuries in the head/neck, chest, abdomen, and pelvis. Regional and total TDV scores were compared between patients that did or did not develop MOF or sustained SIRS. The magnitude of organ dysfunction was also stratified by the magnitude of TDV. Results Mean total and pelvic TDV scores were significantly increased in patients who developed MOF. Mean total, chest, and abdominal TDV scores were increased in patients who developed sustained SIRS. The magnitude of organ dysfunction was significantly higher in patients who sustained large volume injuries in the pelvis or abdomen, and in patients who sustained injuries in at least three anatomic regions. Conclusions A novel index that quantifies the magnitude and distribution of mechanical tissue damage volume is a patient-specific index that can be used to identify patients who have sustained injury patterns that predict progression to MOF and SIRS. The preliminary methods will need refinement and prospective validation.