The data assessing the prognostic value of peak exercise oxygen consumption (VO2) in heart failure (HF) patients is largely derived from cross-sectional studies in which medical therapy was not maximized in all eligible patients and no clear explanation was given as to why such was the case. To assess the relative prognostic value of peak VO2 with respect to baseline medical therapy and its potential impact on transplant listing, 1-year event-free (death or left ventricular assist device placement) survival was compared among 341 HF patients, stratified in three groups based on peak VO2 (<10, 10 to 14, and >14 mL/min/kg). Similar analysis was performed on a subset of 288 patients who were on optimal medical therapy within this group. Average age of the study population was 55+/-11 years, ejection fraction was 23%+/-08%, and peak VO2 was 12.4+/-3.6 mL/min/kg. One-year event-free survival for the overall cohort was: peak VO2<10 (n=87), 63.2%; 10 to 14 (n=141), 81.1%; and >14 mL/min/kg (n=113), 90.2%. Patients with the same groups who were on optimal therapy had an event-free 1-year survival as follows: <10 (n=69), 72.4%; VO2 10 to 14 (n=127), 91.5%; and >14 mL/min/kg (n=92), 94.6%. In conclusion, cross-sectional assessment of HF prognosis may be misleading. In the intermediate risk group, this can significantly impact on medical decisions (eg, transplant listing). Optimization of therapy and long-term follow-up by a specialist may impact transplant listing.