Many studies have investigated the clinical accuracy of the D-dimer test in combination with pretest probability score for deep venous thrombosis (DVT) exclusion. However, few have evaluated its potential when combined with additional markers such as fibrin monomer. The aim of this study was to test the incremental usefulness of fibrin monomer for DVT screening in a bi-marker approach. This was achieved by adding the fibrin monomer to logistic models that included different D-dimer tests. Plasma concentrations of D-dimer and fibrin monomer were measured in 96 outpatients suspected of having DVT and in 76 patients selected from the total patient group according to pretest probability score (termed the DVT-unlikely group). We constructed receiver operating characteristic curves for three different D-dimer assays. Predictive probabilities from different logistic regression models and pair-wise comparisons of the areas under the receiver operating characteristic curve (AUCs) were calculated without and with fibrin monomer included in the models. For all three D-dimer assays, the AUCs were higher in the DVT-unlikely group compared with AUCs in the total patient group [but the differences were without statistical significance (P > 0.05)]. The calculated fibrin monomer AUCs (0.724 in the total patient group and 0.683 in the DVT-unlikely group) were lower than the D-dimer tests' AUCs. The AUCs obtained from logistic regression models that included the three D-dimer tests in the total patient group and the DVT-unlikely group were significantly increased when fibrin monomer was included in the model to such an extent that the AUCs for one of them indicated outstanding discriminative abilities. Simultaneous D-dimer and fibrin monomer determination provides a more valuable approximation for DVT exclusion compared with just D-dimer analysis. Bearing in mind that the fibrin monomer assay is now both more practical and more suited for routine clinical use, fibrin monomer determination could be a more commonly used parameter together with D-dimer and pretest probability score for DVT diagnosis in the future.