Peak exercise oxygen consumption (VO2, in mL/min/kg) is a reliable prognostic marker in heart failure (HF). Anemia, which is common in HF, affects both exercise capacity and prognosis. In this study, we assessed the relationship between peak VO2 and prognosis among HF patients with and without anemia. Data on 344 HF patients were divided into three groups based on peak VO2 (<10, 10 to 14, and >14). Each group stratified by the presence of anemia (<13 mg/dL in men and <12 mg/dL in women) was compared for death or left ventricular assist device (LVAD) placement, and death or LVAD or transplantation. The mean patient age was 53.4+/-11.8 years; hemoglobin level, 12.8+/-1.8 mg/dL; and average follow-up, 629+/-459 days. Overall 32% of patients were anemic. The presence of anemia significantly impacted outcomes among patients with peak VO2<10, namely 42.2% versus 18.9% death or LVAD need (P=.01) and 66.7% versus 43.3% death or LVAD or transplantation (P=.06) for anemic versus nonanemic patients, respectively. The prognosis was similar among groups with higher peak VO2. After adjusting for baseline differences, anemic patients with peak VO2<10 were at higher risk for adverse outcomes: odds ratio (OR) 3.69 (95% confidence interval [95% CI] 1.31 to 9.87) for death or LVAD; and OR 5.67 (95% CI=1.42 to 19.4) for death or LVAD or transplant. Anemia significantly impacted the prognosis of HF patients with peak VO2 less than 10 mL/min/kg. Since these patients are most likely to be evaluated for transplantation, the presence of anemia may further help to stratify prognosis in this group.