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Injury Severity Score (ISS) is commonly used in prediction models and risk adjustment for mortality. However, few studies have assessed the relationship of ISS to outcomes such as resource use. To test the utility of ISS for investigation of the quality of trauma care, we evaluated the impact of ISS on resource utilization and mortality.Of 1,895,249 cases from a Japanese administrative database in 2006, 13,627 trauma patients with ISS were analyzed. Variables included demographics, ISS, number and locations of injured organs, comorbidities, diagnostic and therapeutic procedures recorded during hospitalization, and hospital type. Dependent variables were length of stay (LOS), total charges (TC), initial 48-hour TC, high outliers of LOS or TC, and mortality. Multivariate analyses were used to measure the impact of ISS.ISS 1 to 9 was most frequent (85.5%) and blunt injury occurred in 93.7% of patients. With increasing ISS, the mortality rate rose to 27.2% at ISS ≥36. LOS was higher at ISS ≥36 whereas TC was higher at 25 to 35. After controlling for study variables, rehabilitation was most strongly associated with LOS, TC, and LOS outliers. ISS 25 to 35 affected initial 48-hour TC most, while ventilation affected mortality most. “Abdomen, pelvic organs” and ISS 25 to 35 or ≥36 were more strongly associated with outcomes.Specific ISS and injured organs may be used to estimate resource use or mortality for monitoring quality of trauma care. To integrate a more efficient system of trauma care, variations in resource input among hospitals should be investigated.