OBJECTIVES: Deep vein thrombosis (DVT) is associated with a high degree of morbidity and requires rapid diagnosis and effective anticoagulant treatment. An accurate diagnosis of DVT requires clinical assessment e.g. calculation of pretest-probability score (PTP) and objective testing, because the clinical features are non-specific and commonly used imaging techniques can be inconclusive. The use of D-dimer assays improves diagnostic accuracy. The aim of this study was to examine the cost-effectiveness of three different D-dimer assays in the diagnosis of DVT, alone or in combination with PTP. METHODS: We construct two decision-analytic models (DAM) involving 96 outpatients with clinically suspected acute DVT. First DAM involve 96 outpatients and estimate the number needed to screen to find one true positive patients (NNSTPP) selected for compression ultrasound (CUS) and costs of three strategies: DVT screening with D-dimer Plus assay; DVT screening with D-dimer Hemosil assay and DVT screening with Vidas D-dimer Exclusion assay. Second DAM involves 79 patients selected from the 96 patients according to PTP scoring and estimate NNSTPP and costs of three strategies as for previous model. The cost of strategies was calculated on the basis of the consumed resources for diagnostic tests, laboratory time and consumables. RESULTS: The perspective of incremental cost-effectiveness analysis is the clinical laboratory setting. A diagnostic strategy employing DVT screening with Vidas D-dimer Exclusion assay had lowest cost per additionally successfully diagnosed patient than the strategy employing DVT screening with D-dimer Hemosil assay in the first DAM (€1.13 vs. 19.15) and second DAM (€8.7 vs. 20.9). CONCLUSIONS: In the clinical laboratory setting is sufficient to determine D-dimer concentration with Vidas D-dimer Exclusion assay for DVT screening. A diagnostic strategy using PTP assessment and Vidas D-dimer Exclusion assay effectively diagnoses DVT, but expands costs per additionally successfully diagnosed patient.