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The purpose of this study was to evaluate the effects of ambulance driving distance and transport time on mortality among trauma incidents occurring in the City of Chicago, a large metropolitan area.We studied individuals 16 years or older who suffered a Level I or II injury and were taken to a Level I trauma center. The outcome was in-hospital mortality, including those dead on arrival but excluding those deemed dead on scene. Driving distance was calculated from the scene of injury to the trauma center where the patient was taken. Transport time was defined as the time from scene departure to arrival at the trauma center. Covariates included injury severity measures recorded at the scene. Logistic regression and instrumental variable probit regression models were used to examine the association between driving distance, transport time, and mortality, adjusting for injury severity.A total of 24,834 incidents were analyzed, including 1,464 deaths. Median driving distance was 3.9 miles, and median transport time was 13 minutes. Our findings indicate that increased driving distance is associated with a modest increase in mortality, with a covariate-adjusted odds ratio of 1.12 per 2-mile increase in distance (95% confidence interval [CI], 1.05–1.20). This corresponds to an increase in overall mortality of 0.26 percentage points per 2 miles (95% CI, 0.11–0.40). Using distance as an instrumental variable, we estimate a 0.51 percentage point increase in mortality per 5-minute increase in transport time (95% CI, 0.14–0.89).We find a modest effect of distance on mortality that is approximately linear over a range of 0 to 12 miles. Instrumental variables analysis indicated a corresponding increase in mortality with increasing transport time. Limitations of the study include the possibility of unmeasured confounders and the assumption that distance affects mortality only through its effect on transport time.Prognostic study, level III.