Acute pulmonary embolism (PE) is a cardiovascular challenge with potentially fatal consequences.This study was designed to observe the association of novel cardiac biomarkers with outcome in this setting. In this prospective study, from 86 patients with a confirmed diagnosis of PE, 59 patients met the inclusion criteria (22 men, 37 women; mean age, 63.36±15.04 y). The plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), tenascin-C, and D-dimer were measured at the time of confirmed diagnosis. The endpoints of the study were defined as the short-term adverse outcome and long-term all-cause mortality.Totally, 11.8% (7/59) of the patients had the short-term adverse outcome. The mean value of logNT-proBNP was 6.40±1.66 pg/ml. Among all the examined biomarkers, only the mean value of logNT-proBNP was significantly higher in the patients with the short-term adverse outcome (7.88±0.67 vs 6.22± 1.66 pg/ml; OR, 2.359; 95% CI, 1.037 to 5.367; p=0.041). After adjustment, a threefold increase in the short-term adverse outcome was identified (OR, 3.239; 95% CI, 0.877 to 11.967; p=0.078). Overall, 18.64% (11/59) of the patients had expired by the long-term follow-up. Moreover, adjustment revealed an evidence regarding association between increased logNT-proBNP levels and longterm mortality (HR, 2.163; 95%CI, 0.910 to 5.142; p=0.081).Our study could find evidences on association between increased level of NT-proBNP and short-term adverse outcome and/or long-term mortality in PE. This biomarker may be capable of improving prediction of outcome and clinical care in non-high-risk PE.