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The association between tranexamic acid (TXA) and fibrinolysis shutdown is unknown. We hypothesize that TXA is associated with fibrinolysis shutdown in critically injured trauma patients.Two hundred eighteen critically injured adults admitted to the intensive care unit at an urban Level I trauma center from August 2011 to January 2015 who had thromboelastography performed upon intensive care unit admission were reviewed. Groups were stratified based on fibrinolysis shutdown, which was defined as LY30 of 0.8% or less. Continuous variables were expressed as mean ± standard deviation or median (interquartile range). Poisson regression analysis was used to determine predictors of shutdown.Patients were age 46 ± 18 years, 81% male, 75% blunt trauma, Injury Severity Score of 28 ± 13, 16% received TXA, 64% developed fibrinolysis shutdown, and mortality was 15%. In the first 24 hours, 4 (2–9) units packed red blood cells and 2 (0–6) units fresh frozen plasma were administered. Those with shutdown had worse initial systolic blood pressure (114 ± 38 mm Hg vs. 129 ± 43 mm Hg, p = 0.006) and base deficit (−5 ± 6 mEq/L vs −3 ± 5 mEq/L, p = 0.013); received more packed red blood cells [6 (2–11) vs. 2 (1–5) units, p < 0.0001], and fresh frozen plasma [3 (0–8) vs. 0 (0–4) units, p < 0.0001]; and more often received TXA (23% vs. 4%, p <0.0001). After controlling for confounders, TXA (relative risk, 1.35; 95% confidence interval, 1.10–1.64; p = 0.004) and cryoprecipitate transfusion (relative risk, 1.29; 95% confidence interval, 1.07–1.56; p = 0.007) were independently associated with fibrinolysis shutdown.Patients who received TXA were at increased risk of fibrinolysis shutdown compared with patients who did not receive TXA. We recommend that administration of TXA be limited to severely injured patients with evidence of hyperfibrinolysis and recommend caution in those with evidence of fibrinolysis shutdown.Therapeutic, level III.