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Introduction: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aimed to compare markers of coagulation between male and female trauma patients across different ages., Methods: Secondary analysis of a prospective cohort study that was conducted at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry measurement. Trauma patients were divided into four categories: males younger than 45 years, males 45 years or older, females younger than 45 years, and females 45 years or older. In a sensitivity analysis, patients between 45 and 55 years old were excluded to control for menopausal transitioning. Groups were compared with a Kruskal-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality., Results: A total of 1,345 patients were available for analysis. Compared with the other groups, mortality was highest in females 45 years or older, albeit not independent from injury severity and shock. In the group of females 45 years or older, there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1,104 patients demonstrated an independent relationship between female sex, age 55 years or older, and mortality. Rotational thromboelastometry profiles did not reflect the changes in coagulation tests., Conclusion: Female trauma patients past their reproductive age have an increased risk of mortality compared with younger females and males, associated with augmented fibrinolysis and clotting factor consumption. Rotational thromboelastometry parameters did not reflect coagulation differences between groups., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)