The fibrin-related markers (FRMs), including soluble fibrin (SF), D-dimer and fibrin and fibrinogen degradation products (FDP) are considered to be useful for the diagnosis of thrombosis; however, evidence for the diagnosis of thrombosis by SF is still not well established. The present study was designed to evaluate the usefulness of SF in the diagnosis of venous thromboembolism (VTE). The plasma concentrations of FRMs were measured in 551 in-patients suspected to have a VTE. The plasma levels of SF, D-dimer and FDP were significantly higher in patients with VTE than patients without VTE and those were significantly higher in patients without VTE than in healthy volunteers. In a receiver operating characteristic analysis for the diagnosis of VTE, the area under the curve was 0.950 for SF, 0.933 for FDP and 0.805 for D-dimer. The appropriate cut-off values for the diagnosis were as follows SF 5.9 microg/ml, FDP 2.1 microg/ml and D-dimer 4.8 microg/ml. To obtain a 100% negative predictive value for the diagnosis of VTE, the SF was less than 5.2 microg/ml, FDP was less than 1.3 microg/ml, and D-dimer was less than 0.5 microg/ml. Our findings suggest that the SF assay is useful for the diagnosis and exclusion of VTE.