D-dimer assays are sensitive but have poor specificity. False positive results lead to extra imaging and hospital admissions.To make a pilot comparison of the diagnostic accuracy of the standard quantitative latex HemosIL D-dimer assay with a newer HemosIL D-dimer HS version designed to have improved specificity.Consecutive patients presenting from the community to an Emergency Department that were investigated for suspected pulmonary embolism using a D-dimer test were included in the study. Standard and D-dimer HS tests were performed. Pulmonary Embolism was diagnosed on the basis of imaging studies or post-mortem at any time from presentation to 90 days thereafter.The prevalence of Pulmonary Embolism was 4.5% (18/402). The sensitivity, specificity, negative predictive value, and positive predictive value for the standard quantitative D-dimer test was 100% (81.5 – 100.0), 49.2% (44.1 – 54.3),100% (98.1 – 100.0), and 8.5% (5.1 – 13.0), respectively, and 100% (81.5 – 100.0), 58.3% (53.2 – 63.3),100% (98.4 – 100.0), and 10.1% (6.1 – 15.5), for the D-dimer HS test. There were 35 (16%) fewer ‘false positives’ using the D-dimer HS assay compared with the standard assay.D-dimer HS has superior specificity to the standard quantitative D-dimer test without any loss of sensitivity. The generation of fewer false positive results should lead to less unnecessary diagnostic imaging; the use of which is associated with increased hospital admissions and length of stay. The HS assay may therefore have significant health economic benefits.