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Patients suspected of having venous thromboembolism (VTE), with a low pretest probability, undergo D-dimer testing. A negative D-dimer, in a low-risk patient rules out VTE with a high degree of certainty because of its high sensitivity. It is, however, a poorly specific test, and the absolute value increases with age. The aim of this study was to establish whether an age-adjusted D-dimer could be safely used instead of a standard cut-off level in low-risk patients over the age of 50 years.This was a retrospective review of 1649 patients with suspected VTE whose D-dimer levels were analysed. In low-risk patients (defined as ‘VTE unlikely’ using the dichotomized Wells’ scores), the outcomes in terms of confirmed VTE diagnosis, hospital admission and investigations using an age-adjusted D-dimer level (measured in D-dimer units) of 5× the age for patients over 50 years of age and 250 ng/ml for patients younger than 50 years of age, was compared with the cut-off standard level (230 ng/ml in all patients).Of the total group of patients in the VTE unlikely group, the proportion of patients with a negative D-dimer when using the standard cut-off was 64.9% (859/1324). A further 130 patients had a negative D-dimer when the age-adjusted cut-off was used, increasing the proportion of all patients in whom VTE could be excluded without imaging to 74.7% (989/1324).For those patients of 75 years or older, the proportion of patients in whom VTE could be excluded without imaging increased from only 91/242 (37.6%) when using the standard D-dimer cut-off to 154/242 (63.6%) when the age-adjusted cut-off was used.These changes occurred without any additional false-negative findings.For patients over the age of 50 years suspected of having VTE with a low pretest probability, increasing the D-dimer cut-off level to 5× the age increases the proportion of patients in whom VTE can safely be excluded without radiological imaging.