Objectives: To characterize contemporary use of tranexamic acid (TXA) in combat injury and to assess the effect of its administration on total blood product use, thromboembolic complications, and mortality. Design: Retrospective observational study comparing TXA administration with no TXA in patients receiving at least 1 unit of packed red blood cells. A subgroup of patients receiving massive transfusion (≥10 units of packed red blood cells) was also examined. Univariate and multivariate regression analyses were used to identify parameters associated with survival. Kaplan-Meier life tables were used to report survival. Setting: A Role 3 Echelon surgical hospital in southern Afghanistan. Patients: A total of 896 consecutive admissions with combat injury, of which 293 received TXA, were identified from prospectively collected UK and US trauma registries. Main Outcome Measures: Mortality at 24 hours, 48 hours, and 30 days as well as the influence of TXA administration on postoperative coagulopathy and the rate of thromboembolic complications. Results: The TXA group had lower unadjusted mortality than the no-TXA group (17.4% vs 23.9%, respectively; P=.03) despite being more severely injured (mean [SD] Injury Severity Score, 25.2 [16.6] vs 22.5 [18.5], respectively; P<.001). This benefit was greatest in the group of patients who received massive transfusion (14.4% vs 28.1%, respectively; P=.004), where TXA was also independently associated with survival (odds ratio=7.228; 95% CI, 3.016-17.322) and less coagulopathy (P=.003). Conclusions: The use of TXA with blood component - based resuscitation following combat injury results in improved measures of coagulopathy and survival, a benefit that is most prominent in patients requiring massive transfusion. Treatment with TXA should be implemented into clinical practice as part of a resuscitation strategy following severe wartime injury and hemorrhage.