Background: Abnormal ventilatory/hemodynamic responses to exercise contribute to functional impairment in patients with heart failure (HF). This study investigates how interval and continuous exercise regimens influence functional capacity by modulating ventilatory efficiency and hemodynamic function in HF patients. Methods: Forty-five HF patients were randomized to perform either aerobic interval training (AIT; 3-minute intervals at 40% and 80% VO2peak) or moderate continuous training (MCT; sustained 60% VO 2peak) for 30 min/day, 3 days/week for 12 weeks, or to a control group that received general healthcare (GHC). A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics, whereas a near-infrared spectroscopy was employed to assess perfusion/O2 extraction in frontal cerebral lobe (â̂†[THb]FC / â̂†[HHb]FC) and vastus lateralis (â̂†[THb]VL / â̂†[HHb] VL), respectively. Results: Following the 12-week intervention, the AIT group exhibited higher oxygen uptake efficiency slope (OUES) and lower VE-VCO2 slope than the MCT and GHC groups. Furthermore, AIT, but not MCT, boosted cardiac output (CO) and increased â̂ †[THb]FC, â̂†[THb]VL, and â̂†[HHb]VL during exercise. In multivariate analyses, CO was the dominant predictor of VO2peak. â̂†[THb]FC and â̂†[THb] VL, which modulated the correlation between CO and OUES, were significantly correlated with OUES. Simultaneously, â̂†[THb] VL was the only factor significantly associated with V E-VCO2 slope. Additionally, AIT reduced plasma brain natriuretic peptide, myeloperoxidase, and interleukin-6 levels and increased the Short Form-36 physical/mental component scores and decreased the Minnesota Living with Heart Failure questionnaire score. Conclusions: AIT effectively improves oxygen uptake efficiency by enhancing cerebral/muscular hemodynamics and suppresses oxidative stress/inflammation associated with cardiac dysfunction, and also promotes generic/disease-specific qualities of life in patients with HF. © 2011 Elsevier Ireland Ltd.