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Abstract: Introduction: D-dimer is commonly used in the workup of suspected Pulmonary Embolism (PE), but its specificity decreases with age. We evaluated whether using a higher cutoff value for D-dimer could increase the test specificity without reducing its sensitivity for ruling-out PE in elderly and very elderly patients presenting to the Emergency Department (ED). Material and Methods: All patients with D-dimer and pulmonary Computed Tomography Angiography (CTA) performed in the ED of Vimercate Hospital, from 2010 through 2012 for clinical suspicion of PE were included in this retrospective cohort study. Results: Study population 481 patients (63.4% women, mean age 73.0±16.1years, confirmed PE 22.5%). In very elderly patients (aged 80 or more years, n=191), compared with standard 490ng/mL D-dimer threshold, both higher fixed (1000ng/mL) and age-adjusted cutoffs increase the specificity of D-dimer for the exclusion of PE maintaining a Negative Predictive Value of 100%. Potentially avoided CTAs were 12(6.3%) using 1000ng/mL cutoff and 10(5.2%) age-adjusted. In very elderly patients the Number Needed to Test was incalculable for the standard cutoff (0 cases), 16 for 1000ng/mL and 19 for age-adjusted. In patients with PE, index episode mortality was 6.5%, and death occurred only in subjects with D-dimer values above 1000ng/mL and age-adjusted thresholds. Conclusion: For very elderly patients with suspected PE in ED, both higher fixed D-dimer (1000ng/mL) and age-adjusted thresholds increase test specificity for excluding PE without reducing its sensitivity, leading to a safe reduction in the number of CTAs. [Copyright &y& Elsevier]