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 long-term 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.