Summary. Background: A number of variables have been evaluated for risk stratification in patients with acute pulmonary embolism (PE). Whereas increased D-dimer levels have been associated with mortality at 3 months, its role in predicting short-term outcome (the period of time during which any therapeutic decision has to be taken) remains unclear. Methods: RIETE is an ongoing, prospective registry of consecutive patients with acute venous thromboembolism. We assessed the prognostic value of D-dimer levels at baseline, measured with an automated latex agglutination test (IL Test D-dimer®), on the 15-day outcome in patients with acute PE. Overall mortality, fatal PE and major bleeding rates were compared by quartile. Results: As of February 2008, 1707 patients with acute PE underwent D-dimer testing. Of these, 72 patients (4.2%) died during the first 15 days, 11 (0.6%) had recurrent PE, and 29 (1.7%) had major bleeding. Overall mortality increased with increasing D-dimer levels, from 2.7% in the first quartile (< 1050 ng mL−1) to 7.0% in the fourth quartile (≥ 4200 ng mL−1). The rates of fatal PE and major bleeding also increased. On multivariate analysis, patients with D-dimer levels in the fourth quartile had an increased risk for overall death (odds ratio, 1.8; 95% CI, 1.1–3.2), fatal PE (odds ratio, 2.0; 95% CI, 1.0–3.8) or major bleeding (odds ratio, 3.2; 95% CI, 1.5–7.0). Conclusions: PE patients with D-dimer levels in the fourth quartile had an increased incidence of overall death, fatal PE and major bleeding within 15 days both before and after multivariate adjustment.