Objective: To assess the clinical outcome of patients suspected of pulmonary embolism (PE) following implementation of an emergency department (ED) diagnostic guideline. Methods: A prospective observational study of all patients suspected of PE who presented to the ED during a four-month study period. The authors' modification of the Charlotte criteria recommended D-dimer testing in those younger than 70 years of age with a low clinical suspicion of PE and no unexplained hypoxemia, unilateral leg swelling, recent surgery, hemoptysis, pregnancy, or prolonged duration of symptoms. The primary outcome was the identification of venous thromboembolism during a three-month follow-up period. The negative predictive value of the overall diagnostic strategy and the test characteristics of D-dimer were calculated. Results: A total of 1,207 consecutive patients were evaluated for suspected PE; 71 (5.8%) were diagnosed with venous thromboembolism. One missed case of PE was identified on follow-up, yielding a negative predictive value of 99.9% (95% confidence interval [CI] = 99.5% to 100%). The missed case was a patient who presented with pleuritic chest pain and shortness of breath; a chest radiograph revealed pneumothorax, and the physician decided not to pursue the positive D-dimer result. The patient returned six weeks later with PE. Subgroup analysis of patients having D-dimer performed (n= 677) yields a sensitivity of 0.93 (95% CI = 0.77 to 0.98) and a specificity of 0.74 (95% CI = 0.70 to 0.77). Conclusions: Implementation of a PE diagnostic guideline in a community ED setting is safe and has improved the specificity of the enzyme-linked immunosorbent assay D-dimer test when compared with previous studies.