Cross-linked fibrin degradation products have been used to detect venous thrombosis. While the sensitivity of plasma D-dimer measured by ELISA in the diagnosis of deep vein thrombosis (DVT) is high, the utility of ELISA methods is limited in a clinical setting. This study analysed the diagnostic value of a rapid D-dimer assay performed on whole blood samples (SimpliRed D-dimer) compared with latex and ELISA in 86 patients suspected of having DVT. SimpliRed D-dimer was positive in 47/50 of patients with DVT established by Doppler ultrasound (DU; sensitivity 94%). SimpliRed D-dimer was positive in 35/37 of patients with proximal DVT, nine out of nine with popliteal DVT and three out of four with superficial thrombophlebitis. The specificity of SimpliRed D-dimer in the diagnosis of DVT was 61%. The sensitivity of the SimpliRed D-dimer assay was at least comparable with the ELISA (87%) and superior to the latex assay (80%). The positive predictive value (77%), the negative predictive value (88%) and the overall accuracy (80%) of the SimpliRed assay were better than the ELISA and latex methods. It is concluded that SimpliRed D-dimer is a rapid useful assay for screening of patients suspected of having deep vein thrombosis.