Objectives: Our aim was to determine the effect of β-adrenergic blockade on the prognostic value of peak oxygen consumption testing in patients with heart failure. Background: Peak oxygen consumption has been shown to be a useful prognostic tool in patients with heart failure. However, studies demonstrating the utility of peak oxygen consumption were conducted before β-blocker therapy became widespread. Thus, our objective was to determine the effect of β-blockers on the prognostic value of peak oxygen consumption in patients with heart failure. Methods: Actuarial, anthropomorphic, hemodynamic and exercise ventilatory data were collected from 369 patients with heart failure. Death and orthotopic heart transplants were the events tracked. Patients were divided into those taking β-blockers and those not taking them. Event-free survival days were calculated. Results: One hundred ninety-nine patients on β-blockers and 170 not on β-blockers were studied. There were 40 orthotopic heart transplants and 82 deaths during follow-up. Peak oxygen consumption (milliliters per kilogram per minute) trended toward being an independent predictor of event-free survival (p = 0.055). In patients on and not on β-blockers, a peak oxygen consumption of >14 ml/kg·min was associated with a 1-year event rate of approximately half of that associated with a peak oxygen consumption ≤14 ml/kg·min. However, for every level of peak oxygen consumption, the event rate was lower in the group taking β-blockers. Conclusions: β-blocker status does not change the predictive power of peak oxygen consumption in patients with heart failure, but β-blocker status is important to consider when using peak oxygen consumption to predict event-free survival in patients with heart failure.