As D-dimer level remains elevated in a significant proportion of patients after completion of a 6-month anticoagulant course for a first episode of venous thromboembolism (VTE), the clinical usefulness of D-dimer for ruling out a possible recurrence might be limited. In 1721 consecutive patients presenting in the emergency department with clinically suspected pulmonary embolism (confirmed in 24%), the D-dimer test result was negative in 33% of patients without previous VTE but was negative in only 16% of patients with a previous thromboembolic event (P<.001). The 3-month thromboembolic risk was 0% (95% confidence interval, 0.0%-7.9%) in patients with previous VTE and a negative D-dimer test result. The 2-fold lower chance of obtaining a negative D-dimer test result in patients with previous VTE was independent of older age, active malignancy, fever, and recent surgery. Therefore, in patients suspected of pulmonary embolism with a previous thromboembolic event, a negative D-dimer test result appears to safely rule out a recurrent event. However, owing to lower proportion of negative results in such patients, the clinical usefulness of D-dimer testing is somewhat reduced.