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It is unclear whether cardiopulmonary stress testing provides prognostic information in patients with very advanced heart failure receiving contemporary medical therapy. Analysis of cardiopulmonary treadmill stress data in a group of patients with advanced heart failure and severe functional impairment was performed (N=102, peak exercise oxygen consumption [VO2] ≤14 mL/kg/min, 47% receiving β‐blockers). Dynamic variables (peak ‐ baseline values) better predicted outcomes than did single value peak measurements, especially ΔVO2. Multivariate analysis showed that usage of β‐blockers and ΔVO2 (both P<.05) independently and significantly predicted outcomes. Subgroup analysis showed that ΔVO2 was particularly useful in predicting outcomes in patients with ischemic cardiomyopathy or who were not receiving β‐blockers. Thus, in patients with very advanced heart failure, cardiopulmonary stress testing‐derived ΔVO2 provides important prognostic information useful to help predict clinical deterioration or death, particularly for patients with ischemic cardiomyopathy or who are not receiving β‐blockers.