Coagulation factor XIII (FXIII) is a factor in the coagulation cascade whose activation leads to the binding of fibrin and fibrinolysis inhibitors into a fibrin clot that is less susceptible to fibrinolysis. FXIII deficiency can be the result of a hereditary or acquired disorder and leads to prolonged bleeding. The hereditary form is a rare coagulation disease with a prevalence of 1 in 2 million people. Acquired deficiency is the more common form and is characterized by autoimmunity or increased consumption of FXIII. Patients with FXIII deficiency are treated with FXIII replacement therapy, which prevents or stops bleeding. In this paper, we retrospectively analyzed the indication for the use of FXIII concentrate at the University Hospital Centre Zagreb, in the period from January 2020 to March 2021. We acquired demographic data, the diagnosis of admission to the hospital, the indication for the use of FXIII concentrate, the treatment outcome, and the clinic where patients were treated. A total of 24 patients received FXIII concentrate in the mentioned period. The most common diagnoses were aortic aneurysm, leukemia, and lymphoma, disseminated intravascular coagulopathy, liver cirrhosis and kidney failure. As an indication for FXIII concentrate therapy, 21 of them (87.5%) had some form of bleeding, while 10 (41.67%) met the criteria for massive bleeding. The percentage of mortality was 54.2%. FXIII activity was determined in 16 (66.7%) patients before therapy and was decreased in all patients with determined FXIII activity. FXIII deficiency is an underdiagnosed clinical entity, often due to normal coagulation parameters, and its replacement can improve the clinical picture and patient outcome.