INTRODUCTION Endothelial dysfunction has been reported to be involved in the pathogenesis of inflammatory bowel disease (IBD) and concomitant thromboembolic complications. Inflammation stimulates the expression of tissue factor and tissue factor pathway inhibitor (TFPI) by endothelial cells. OBJECTIVES This study assessed the relationship between TFPI levels and disease activity in patients with IBD. PATIENTS AND METHODS A total of 50 consecutive adult patients with ulcerative colitis (UC), 50 patients with Crohn disease (CD), and 50 healthy controls were enrolled to the study. Plasma levels of total TFPI, free TFPI, and von Willebrand factor were measured. Associations among these levels, disease activity, and inflammatory marker levels were assessed. RESULTS Total TFPI levels were higher in patients with IBD (median, 68.5 [IQR, 60.2-80.1] ng/ml) than in controls (median, 61.1 ng/ml [IQR, 54.3-74.2]; P = 0.01). Free TFPI levels were higher in patients with active UC (median, 12.8 ng/ml [IQR, 11.1-15.4]), inactive UC (median, 9.9 ng/ml [IQR, 7.3-11.5]), active CD (median, 11.7 [IQR, 9.7-14.4] ng/ml), and inactive CD (median, 9.7 ng/ml [IQR, 8.6-11.6]) than in controls (median, 5.5 ng/ml [IQR, 4.3-7.2]; P <0.001). In the CD and UC groups, free TFPI levels correlated with the levels of inflammatory markers and disease activity. The von Willebrand factor level was higher in patients with UC (median, 143.4 IU/dl [IQR, 115.5-170.4]) and those with CD (median, 151.8 IU/dl [IQR, 112.8-189.4]) than in controls (85.1 IU/dl [IQR, 77.1-101.5]; P <0.001 for both comparisons). CONCLUSIONS The anticoagulant TFPI pathway is activated during remissions and flares in patients with IBD. The free TFPI level correlates with biochemical markers of inflammation and disease activity.