Background: Anemia disturbs hemorheological/hemodynamic properties, whereas aerobic interval training (AIT) achieves a superior aerobic fitness in patients with heart failure (HF). This study investigated whether AIT influences functional capacity by modulating hemorheological/hemodynamic functions in HF patients with/without anemia. Methods: Sixty HF patients were divided into non-anemic (HF-NA, hemoglobin≧12 g/dL in women/≧13 g/dL in men; n=30) and anemic (HF-A, hemoglobinb11 g/dL in women/b12 g/dL in men; n=30) groups, and 30 normal counterparts were enrolled as a control group. These HF patients performed AIT (3-minute intervals at 40% and 80%VO2peak) on a bicycle ergometer for 30 min/day, 3 days/week for 12 weeks. Erythrocyte rheological and central/peripheral hemodynamic characteristics were determined by slit-flow ektacytometer and bioreactance-based device/near infrared spectrometer, respectively. Results: In both HF-NA and HF-A groups, the AIT regimen 1) reduced blood senescent/spherical erythrocyte counts, 2) diminished the values of critical shear stresses for disaggregation and half-maximal deformation of erythrocytes, 3) enhanced cardiac output during exercise, 4) heightened VO2peak and O2 uptake efficiency slope (OUES), and 5) decreased plasma myeloperoxidase and interleukin-6 levels. However, AIT increased the amounts of blood distributed to the frontal cerebral lobe and vastus lateralis muscle during exercise in HF-NA group but not in HF-A group. Additionally, HF-A group exhibited fewer the enhancements of VO2peak and OUES caused by AIT than HF-NA group did. Conclusion: AIT improves aerobic capacity and efficiency by depressing aggregability and enhancing deformability of erythrocytes in patients with HF.However, anemic comorbidity attenuates the adaptations of cerebral/muscular hemodynamic responses to exercise following this regimen. © 2012 Elsevier Ireland Ltd. All rights reserved.