Rationale: Growth-differentiation factor-15 (GDF-15) is a cytokine induced in the heart after ischemia or pressure overload. Circulating levels of GDF-15 provide independent prognostic information in patients with acute coronary syndromes or heart failure. Objectives: We investigated the prognostic value of GDF-15 in acute pulmonary embolism. Methods: In a prospective cohort study, plasma levels of GDF-15 were determined by immunoradiometric assay in 123 consecutive patients with confirmed acute pulmonary embolism. Measurements and Main Results: GDF-15 concentrations on admission ranged from 553 to 47274 ng/L; 101 patients (82%) had GDF-15 levels above the upper limit of normal (1200 ng/L). Patients who suffered pulmonary embolism-related complications during the first 30 days had higher baseline levels of GDF-15 (median, 6039 [25^th to 75^th percentiles, 2778 to 19772] ng/L) compared to those with an uncomplicated course (median, 2036 [25^th to 75^th percentiles, 1279 to 3176] ng/L; P<0.001). By multivariable logistic regression analysis, which included clinical characteristics, cardiac biomarkers (troponin T and NT-proBNP), and echocardiographic findings, GDF-15 emerged as an independent predictor of a complicated 30-day outcome (P=0.033). The c-statistic for GDF-15 was 0.84 (95% confidence interval, 0.76-0.90), as compared to 0.72 for cardiac troponin T, and 0.65 for NT-proBNP. The ability of troponin T, NT-proBNP, and echocardiographic findings of right ventricular dysfunction to predict the risk of a complicated 30-day outcome was enhanced by GDF-15. Furthermore, multivariable Cox regression identified baseline levels of GDF-15 as an independent predictor of long-term mortality (P<0.001). Conclusions. GDF-15 is a promising new biomarker for risk stratification of pulmonary embolism.