Background: Although myocardial fibrosis plays an important role in the progression of heart failure (HF), its prognostic impact still remains to be clarified. Methods and Results: A total of 172 consecutive patients with chronic HF, who underwent cardiac catheterization and endomyocardial biopsy between January 2001 and September 2008, were examined. They were divided into 2 groups: HF with preserved ejection fraction (HFPEF; left ventricular ejection fraction [LVEF] ≥50%, n=81); and HF with reduced LVEF (HFREF; LVEF <50%, n=91). The collagen volume fraction (CVF) in biopsy samples was calculated and its prognostic impact examined. Mean follow-up in the HFPEF and the HFREF groups was 41±33 months and 41±26 months, respectively. Although CVF was similar between the 2 groups (1.83±1.54% vs. 2.07±2.35%), CVF was significantly correlated with LV end-diastolic pressure in the HFREF group but not in the HFPEF group. When HF stage was adjusted, the long-term prognosis was comparable between the 2 groups. When the patients were divided into 2 groups according to median CVF, however, severe fibrosis was a significant predictor for all-cause death (P=0.014) and cardiac events (P=0.02) in the HFREF, but not in the HFPEF group. Conclusions: Myocardial fibrosis evaluated on biopsy samples is a useful indicator for long-term survival, suggesting that it may be an important therapeutic target as well. (Circ J 2011; 75: 2605-2613)