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Safe exclusion of pulmonary embolism (PE) is a common problem in acute medicine. Common care pathways usually involve the use of a pre-test probability score with a D-dimer test to aid clinical decision-making. Unfortunately, the specificity of many D-dimer assays decreases with age. This study investigates the role of an age-adjusted D-dimer of 5 x patient's age when the conventional cut-off of the assay is 230 ng/mL. Data was collected retrospectively over a 12-month period from patients who went on to have either computed tomography pulmonary angiography (CTPA) or pulmonary ventilation/perfusion (V/Q) imaging. D-dimers in patients with low or moderate Wells score were analysed for both conventional and age-adjusted cut-offs. The use of an adjusted D-dimer showed a sensitivity of 0.97 (95% CI 0.9–1.0) while the specificity increased from 0.07 (95% CI 0.04–0.11) for the conventional cut-off to 0.32 (95% CI 0.27–0.38) for the age-adjusted cut-off. Using a 5 x patient's age-adjusted D-dimer cut-off is both safe and showed an increased specificity comparable to those published previously on other D-dimer assays.