Background: Factor XIII (F XIII), the last coagulation factor in the clotting cascade, plays a role in mucosal repair. Beneficial effects of F XIII supplementation in severe ulcerative colitis (UC) have been observed. The aim of this study was to relate plasma F XIII activity to the severity of inflammatory bowel disease (IBD). Methods: A transversional and, in part, longitudinal study of F XIII activity and related clotting products was performed in 39 patients with UC, 31 patients with Crohn's disease (CD), and 20 controls. Disease activity was assessed with a combined activity score in UC and with the Dutch Activity Index in CD. Results: F XIII activity was decreased in active UC (p<0.05) and active CD (p < 0.05) and was inversely correlated with severity in both UC (r = -0.30) and CD (r = -0.46). In six patients with UC (15%) and six patients with CD (19%) F XIII activity was below the lower range of normal. In these patients apparent rectal bleeding was only found in severe UC. Hyperhbrinolysis was indicated by elevated levels of D-dimer (p<0.001) notwithstanding increased concentrations of alpha-2 antiplasmin (p<0.05). Conclusions: In active IBD we found decreased plasma F XIII activity and hyperfibrinolysis. Decreased F XIII activity was not associated with apparent rectal bleeding in IBD.