Abstract Background 15-F2t -isoprostane (15-F2t -IsoP), a prostaglandin F2 -like compound, is widely recognized as a biomarker of chronic heart failure. This study investigated the potential role and prognostic significance of plasma 15-F2t -IsoP in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods Plasma 15-F2t -IsoP concentrations were determined in 80 consecutive IPAH patients at the time of their first right heart catheterization, and monitored for 30 ± 12 months. The expression of 15-F2t -IsoP protein in autopsy lung samples was determined by immunohistochemical staining. Results Plasma 15-F2t -IsoP concentrations were significantly increased in patients with IPAH compared with healthy controls (91 pg/ml vs. 30 pg/ml, respectively; P < 0.001). Patients with baseline 15-F2t -IsoP concentrations ≥ 97 pg/ml had a significantly lower survival rate than those with lower baseline concentrations ( P < 0.001). During follow-up, 15-F2t -IsoP concentrations in survivors decreased, whereas concentrations in non-surviving patients increased further ( P < 0.05). Elevated concentrations of 15-F2t -IsoP were correlated with a severity of WHO functional class, lower 6-minute walking distance and mixed venous oxygen saturation, higher mean right atrial pressure and brain natriuretic peptide. Multivariate analysis revealed that the plasma 15-F2t -IsoP concentration was an independent factor associated with mortality. Histological studies showed that the expression of 15-F2t -IsoP was up-regulated in remodeled pulmonary vessels. Conclusions An elevated plasma 15-F2t -IsoP concentration and a further increase during follow-up may be a risk factor for higher mortality in patients with IPAH.