Because of the rapid growth in requests for lower extremity duplex scanning, we tested a new rapid D-dimer assay method, the Miniquant test, for its ability to rule out deep vein thrombosis (DVT) in patient subgroups with the following risk factors: malignancy, postoperative state, and cellulitis. One hundred twenty-six consecutive patients with suspected DVT underwent clinical assessment, D-dimer testing with quantitative Miniquant D-dimer assay, and duplex scanning according to standard criteria for the diagnosis of DVT. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated versus duplex scanning for the various risk factor subgroups. Our results showed that the Miniquant D-dimer assay is useful preselection procedure (high NPV) in selected patient subgroups with suspected proximal DVT, including patients with cellulitis and those without malignancy or postoperative state. This preselection procedure has the potential for avoiding a large proportion of unnecessary duplex scanning, thus saving time and reducing costs.