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Records of 132 consecutive patients with multiple musculoskeletal injuries were examined for the purpose of assessing the relationship between the length of time from injury to the operative stabilization of major fractures and the incidence of adult respiratory distress syndrome (ARDS). To be included in the study patients had to have had at least two major long-bone fractures and a Hospital Trauma Index-Injury Severity Score (ISS) of 18 or higher. Early operative fracture stabilization (STAB) is defined as an operation in the first 24 hours postinjury at which the majority of fractures were stabilized without leaving a spine, pelvis, or femur fracture unstable. A stepwise logistic regression was performed on the data. The dependent variable was the presence or absence of ARDS. The independent variables were age, sex, number of injuries, days to first surgery, early operative fracture stabilization (STAB), units of blood the first week, and ISS and its major components: RESP, ABD, CV, EXT, NS, and SSQ. The two independent variables selected as significant by this procedure were STAB and ISS. For the overall data set, a delay in orthopedic surgery (greater than 24 hours) is associated with a fivefold increase in the incidence of ARDS (p < 0.001). For the more severely injured patients (ISS > 40), the comparable rates are 17% with early surgery and 75% with delayed surgery (p < 0.001). A Chi-square test for association between ARDS and STAB adjusting for changes due to ISS grouping is significant (p < 0.001). In looking at the individual components of ISS it is seen that NS is the only one significantly associated with ARDS (p = 0.007).This study shows that there is a significant increase in the incidence of ARDS associated with a delay in operative stabilization of major fractures in patients with multiple orthopedic injuries. This is particularly true for more severely injured patients (ISS > 40). The ISS is of prognostic value in predicting the incidence of ARDS particularly when evaluating extremity (EXT) and neurologic (NS) injuries in the emergency room.