The measurement of D-dimer can provide useful information to aid in the diagnosis of patients with suspected venous thromboembolism. D-dimer measurement in conjunction with adequate estimation of pretest probability can facilitate the safe discharge of patients with suspected pulmonary embolism and limit unnecessary investigation or anticoagulation. We review clinical decision-making strategies in the diagnosis of pulmonary embolism and propose means to minimize diagnostic error that might arise from knowledge of the D-dimer result prior to clinical assessment.