N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) is well established as a predictor of prognosis in patients with left ventricular dysfunction. Although a similar prognostic significance has been suggested in 1 study of right ventricular failure and idiopathic pulmonary arterial hypertension, NT-pro-BNP has not been assessed as a marker of disease severity in a more heterogenous group of patients with chronic precapillary pulmonary hypertension (PH). Hence, this study assessed plasma NT-pro-BNP and other clinical variables in 61 consecutively recruited patients with various forms of chronic precapillary PH. Right-sided cardiac catheterization and cardiopulmonary exercise testing were performed at baseline, and the prognostic significance of NT-pro-BNP was investigated with a mean follow-up of 25 months. Compared with age-matched controls (n = 10), plasma NT-pro-BNP was significantly greater in those with idiopathic pulmonary arterial hypertension (n = 16), chronic precapillary PH associated with other diseases (n = 26), and chronic thromboembolic disease (n = 19) and was correlated with hemodynamic variables and functional capacity. In 17 medically treated patients, the significant decrease in NT-pro-BNP levels correlated with improved hemodynamics. During follow-up, 15 patients died from cardiopulmonary causes. Baseline NT-pro-BNP was an independent predictor of mortality. Kaplan-Meier survival analysis according to the median value of NT-pro-BNP (168 pmol/L) demonstrated a significantly higher mortality rate in those with supramedian values than in those with low plasma levels (p = 0.010). In conclusion, these findings suggest that in a heterogenous group of patients with chronic precapillary PH, plasma NT-pro-BNP can be used to determine the clinical severity of disease and is independently associated with long-term mortality.