BackgroundThe role of factor XIII (FXIII) in trauma-induced coagulopathy (TIC) is not fully understood.MethodsWe evaluated FXIII supplementation in severely injured patients with persistent bleeding. This was a retrospective case series analysis.ResultsTwenty-four patients received FXIII concentrate within 24 h of admission for bleeding that continued after transfusion of > 6 U red blood cells (RBCs); control patients (n= 27) did not receive FXIII concentrate. Both study groups were similar regarding injury severity score and global coagulation tests, but FXIII activity levels were significantly higher and lactate levels significantly lower in the control group, respectively. The differences in FXIII activity between the groups could be attributed to a more severe trauma-induced coagulopathy in FXIII-deficient patients, as demonstrated by lower fibrinogen and higher lactate levels. The median dose of FXIII concentrate within 24 h of admission was 2500 IU (IQR: 1250–4375). Median 24-h transfusion of RBCs (primary study endpoint) was significantly higher in the FXIII group versus controls (10.0 U, IQR 5–14 U vs. 2, IQR 0–6 U;p< 0.01). Subsequently, while patients were in the intensive care unit, there was no statistically significant difference regarding RBC transfusion anymore and the overall clinical outcomes were similar in both patient groups.ConclusionsThe substitution of FXIII in patients who were more seriously compromised due to higher lactate levels and who presented with initially more severe bleedings than patients in the control group, resulted in a comparable transfusion necessity after 24 h. Thus, we guess that the substitution of FXIII in severely injured patients with ongoing bleeding might have an impact on their clinical outcome.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00068-023-02221-z.