Introduction: While various strategies of fracture fixation in trauma victims have been discussed, the effect of damage control orthopedics (DCO) on significant clinical outcome is inconclusive. We examined the mortality of patients managed with DCO, comparing those without DCO, using a nationwide trauma database.Patients and Methods: We retrospectively identified patients with extremity injury, defined as patients with an Abbreviated Injury Scale (AIS) of ≥2 in an upper or lower extremity, in the database that included more than 200 major hospitals from 2004 to 2016. We included those who were age ≥15 years and underwent ORIF. Patients with missing survival data or invalid vital signs at hospital arrival were excluded. Patient data were divided into DCO or non-DCO groups, and propensity scores were developed to estimate the probability of being assigned to the DCO group, using multivariate logistic regression analyses adjusted for known survival predictors, such as age, vital signs at arrival, Abbreviated Injury Scale in extremity, ISS, presence of vascular injury, surgical procedure before fracture treatment, and transfusion requirement. The primary outcome, in-hospital mortality, was compared between the two groups after propensity score matching. Survival analyses were performed, and hazard ratio was adjusted according to age, systolic blood pressure on arrival, and Injury Severity Score.Results: Of the 19,319 patients included in this study, 4407 (22.8%) underwent DCO. After the propensity score matching, 3858 pairs were selected. In-hospital mortality was significantly lower among patients in the DCO than those in the non-DCO groups (40 [1.0%] vs. 66 [1.7%]; odds ratio = 0.60; 95% confidence interval [CI] = 0.41-0.89; P = 0.01). Survival analyses showed that DCO was independently associated with decreased mortality in patients with extremity injury (adjusted hazard ratio = 0.30; 95% CI = 0.20-0.46; P < 0.01).Conclusions: DCO was associated with decreased in-hospital mortality in patients with major fractures. Further clinical study on DCO by selecting patient population should be considered eventually to develop an appropriate strategy for major fractures. [ABSTRACT FROM AUTHOR]