Background: Pulmonary hypertension (PH) still remains a serious disease, for which the plasma level of brain natriuretic peptide (BNP) and hemodynamic variables (eg, cardiac index: CI) are established prognostic factors. The aim of the present study was to identify new additional prognostic factors of the disorder to improve the management of PH. Methods and Results: The study cohort comprised 136 consecutive PH patients admitted to hospital from 1974 to 2008, all of whom were closely followed every 6-12 months. During the follow-up period of 53.5±4.5 [SEM] months, 47 patients died of cardiopulmonary causes. The patients who were initially treated with monotherapy showed improved pulmonary hemodynamics when subsequently treated with combination therapy. Multivariate analysis showed that BNP and CI were significant and independent prognostic factors in all PH patients. However, in PH patients with low CI at diagnosis, only CI improvement by PH therapy was a significant and independent prognostic factor. Indeed, the patients with low CI at diagnosis (CI <2.5) followed by subsequent normalization in response to therapy (CI ≥2.5) showed a significantly better survival compared with those without such normalization. Conclusions: CI normalization in response to treatment is an independent new prognostic factor of PH in patients with low CI at diagnosis, suggesting the importance of intensive therapy to achieve CI normalization.  (Circ J 2010; 74: 1965 - 1971)