Background: Previous studies suggested that hypofibrinolysis is associated with increased risk of peripheral arterial disease. Thrombin activatable fibrinolysis inhibitor (TAFI) has been identified as an important inhibitor of fibrinolysis. The aim of our study was to assess the role of TAFI in young patients with peripheral arterial disease. Methods: In a single-center case-control study we measured plasma TAFI antigen levels and functional TAFI in consecutive young patients (men 18-45 years and women 18-55 years) with a first manifestation of peripheral arterial disease and compared these with a population-based control group. Results: A total of 47 peripheral arterial disease patients and 141 controls (mean age 43) were included. Intact TAFI antigen levels were significantly higher in patients with peripheral arterial disease (112.4 +/- 21.1%) than in controls (104.9 +/- 19.9%, p = 0.03). The risk of peripheral arterial disease increased with 18% (OR 1.18; CI 1.01-1.34) per 10% increase of TAFI antigen. Functional TAFI levels were slightly higher in patients compared to controls, however this difference was not significant. For individuals with the highest functional TAFI levels, above the 90th percentile, the increased risk for peripheral arterial disease was most pronounced (OR 3.1; CI 1.02-9.41). Conclusion: High TAFI levels are associated with increased risk of premature peripheral arterial disease. (C) 2010 Elsevier Ltd. All rights reserved.