Objective: To quantify the impact of fibrinogencontaining cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured. Design: Retrospective observational study comparing the mortality of4groups: tranexamic acid only, cryoprecipitate only, tranexamicacidandcryoprecipitate,andneithertranexamicacidnorcryoprecipitate. Tobalance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality. Setting: A Role 3 Combat Surgical Hospital in southern Afghanistan. Patients: A total of 1332 patients were identified from prospectively collected UK and US trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n=148), cryoprecipitate (n=168), tranexamic acid/cryoprecipitate (n=258), and no tranexamic acid/cryoprecipitate (n=758). Main Outcome Measure: In-hospital mortality. Results: Injury Severity Scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/ cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P<.001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/ cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42- 0.89; P=.01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P=.02, respectively). The combined tranexamic acid and cryoprecipitate effect vs neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P<.001), reflecting nonsignificant interaction (P=.21). Conclusions: Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock. © 2013 American Medical Association. All rights reserved.