BACKGROUND Dyspnea on exertion is common to both heart failure (HF) and chronic obstructive pulmonary disease (COPD), and it is important to discriminate whether symptoms are caused by HF or COPD in clinical practice. The ventilatory equivalent for carbon dioxide (V̇E/V̇CO2) slope and V̇E intercept (a reflection of pulmonary dead space) are two candidate non-invasive indices that could be used for this purpose. Thus, we compared non-invasive indexes of ventilatory efficiency in patients with HF and preserved or reduced ejection fraction (HFpEF and HFrEF, respectively) or COPD. METHODS Patients with HFpEF (n = 21), HFrEF (n = 20), and COPD (n = 22) patients performed cardiopulmonary exercise testing to volitional fatigue. V̇E and gas exchange were measured via breath-by-breath open circuit spirometry. All data from rest to peak exercise were used to calculate V̇E/V̇CO2 slope and V̇E intercept using linear regression. Receiver operating characteristic (ROC) curves were constructed to determine optimized cutoffs for V̇E/V̇CO2 slope and V̇E intercept to discriminate HFpEF and HFrEF from COPD. RESULTS HFrEF patients had a greater V̇E/V̇CO2 slope than HFpEF and COPD patients (HFrEF: 40 ± 9; HFpEF: 32 ± 7; COPD: 32 ± 7) (p < 0.01). COPD patients had a greater V̇E intercept than HFpEF and HFrEF patients (COPD: 3.32 ± 1.66; HFpEF: 0.77 ± 1.23; HFrEF: 1.28 ± 1.19 L/min) (p < 0.01). A V̇E intercept of 2.64 L/min discriminated COPD from HF patients (AUC: 0.88, p < 0.01), while V̇E/V̇CO2 slope did not (p = 0.11). CONCLUSIONS These findings demonstrate that V̇E intercept, not V̇E/V̇CO2 slope, may discriminate COPD from both HFpEF and HFrEF patients.