The aim of this study was to assess the effect of anemia on mortality in chronic heart failure (CHF). Anemia is frequently observed in patients with CHF, and evidence suggests that anemia might be associated with an increased mortality. A systematic literature search in MEDLINE (through November 2007) for English language articles was performed. In addition, a manual search was performed. We included cohort studies and retrospective secondary analyses of randomized controlled trials whose primary objective was to analyze the association between anemia and mortality in CHF. Of a total of 1,327 initial studies, we included 34 studies, comprising 153,180 patients. Information on study design, patient characteristics, outcome, and potential confounders were extracted. Anemia was defined by criteria used in the original articles. Of the 153,180 CHF patients, 37.2% were anemic. After a minimal follow-up of 6 months, 46.8% of anemic patients died compared with 29.5% of nonanemic patients. Crude mortality risk of anemia was odds ratio 1.96 (95% confidence interval: 1.74 to 2.21, p < 0.001). Lower baseline hemoglobin values were associated with increased crude mortality rates (r = -0.396, p = 0.025). Adjusted hazard ratios showed an increased adjusted risk for anemia (hazard ratio 1.46 [95% confidence interval: 1.26 to 1.69, p < 0.001]). Subgroup analysis showed no significant difference between mortality risk of anemia in diastolic or systolic CHF. Anemia is associated with an increased risk of mortality in both systolic and diastolic CHF. Anemia should, therefore, be considered as a useful prognosticator, and therapeutic strategies aimed to increase hemoglobin levels in CHF should be investigated.