Background: Heart failure with reduced ejection fraction (HFrEF) and chronic obstructive pulmonary disease (COPD) are relatively common conditions with similar symptoms of exercise intolerance and dyspnea. The aim of this study was to compare exercise capacity, ventilatory response, and breathing pattern in patient groups with either advanced HFrEF or COPD before and after exercise training. Methods: An observational study was conducted with parallel groups of 25 HFrEF and 25 COPD patients who took part in 6 wk of inpatient rehabilitation with exercise training. All patients underwent cardiopulmonary exercise tests at the start and end of the training, with resting arterial blood gas measurements. Results: The average peak oxygen uptake (V˙o2) was low at the start of the study but increased significantly after training in both groups, or by 2.2 ± 2.1 mL/kg/min in HFrEF patients and 1.2 ± 2.2 mL/kg/min in COPD patients. At ISO-V˙o2 (ie, same level of V˙o2 in pre- and post-exercise tests), carbon dioxide production (V˙co2) decreased after exercise training in both groups. Similarly, at ISO-V˙E (ie, same level of ventilation), breathing frequency (f) decreased and tidal volume (VT) increased, resulting in an improved breathing pattern (lower f/VT ratio) after training. Conclusion: The findings of this study show that exercise training in severely affected patient groups with HFrEF or COPD led to an increase in maximal exercise capacity, a more favorable breathing pattern, and a diminished V˙co2 during exercise. Therefore, comparisons of V˙co2 and breathing pattern at ISO-levels of V˙o2 or V˙E before and after training are valuable and underutilized outcome measures in treatment studies.