Background: Previous work shows that patients with heart failure patients who have peak oxygen consumption (VO2 peak) >14 ml/kg/min do not derive a survival benefit from cardiac transplantation. However, this was shown before β-blocker therapy for patients with systolic heart failure became common, and β-blockers improve survival in patients with heart failure without changing VO2 peak. Our purpose was to re-evaluate the utility of VO2 peak >14 ml/kg/min as an indicator of the need for cardiac transplantation in patients with heart failure who are taking β-blockers. Methods: Actuarial, hemodynamic, and exercise ventilatory data were collected from 540 patients with heart failure, 256 of whom were taking β-blockers. We tracked death and cardiac transplantation. We stratified the percentage of patients event-free 1 and 3 years after VO2 peak study by their VO2 peak and β-blocker status, and compared 1- and 3-year post-transplant survival (United Network of Organ Sharing [UNOS] data). We also compared total mortality for the patients with heart failure as stratified by β-blocker stats and VO2 peak (excluding the 42 who underwent transplantation) with UNOS post-transplant survival. Results: Patients with heart failure who were receiving β-blockers and whose VO2 peak was ≥12 ml/kg/min had greater 1- and 3-year event-free survival rates (95% confidence intervals, 92.6%-96.6% and 85.8%-96.0%) than did post-transplant patients (83.9%-86.3% and 75.4%-76.6%). However, in patients with heart failure not taking β-blockers, VO2 peak <14 ml/kg/min was associated with worse 3-year survival (38.9 - 62.1%) than that for post-transplant patients. Excluding the 42 patients with heart failure in our study who underwent transplantation and then evaluating survival of the remaining patients with heart failure (not event-free survival) did not substantially change these results. Conclusions: Patients with heart failure who are receiving β-blockers do not derive a survival advantage at 1 and 3 years after cardiac transplantation if VO2 peak is ≥12 ml/kg/min. Patients not taking β-blockers whose VO2 peak is <14 ml/kg/min have superior survival with cardiac transplantation.