OBJECTIVE: to assess the acute effects of non-invasive ventilation (NIV) during high-intensity exercise on heart rate variability (HRV) responses in chronic obstructive pulmonary disease (COPD) and Chronic heart failure (CHF) patients. METHODS: This was randomized, double blinded and controlled study. Fourteen patients with COPD-HF diagnosis were evaluated. The subjects underwent to the following tests: (I) cardiopulmonary exercise testing (CPET) on a cycle ergometer ramp protocol; (II) 7 days after CPET, patients randomly underwent two constant-load exercise (CLE) with NIV or Sham ventilation until tolerance limit, with 80% of the CPET peak load. R-R intervals (RRi) were continuously collected during rest, exercise and in recovery. Time and frequency domain and nonlinear heart rate variability (HRV) indices were obtained. RESULTS: NIV resulted in a decrease of Mean iRR, square root of the mean squared differences of successive RRi (rMSSD), RR tri index and high-frequency (HF), nu (p < 0.05) and increase of Mean HR, low-frequency (LF), nu and LF/HF (p < 0.05) during exercise when compared to rest. In addition, NIV during exercise induced lower rMSSD and Sample Entropy when compared with Sham (p < 0.05). Negative correlation was found between forced expiratory volume in 1 second (FEV(1,) L) vs HF (nu) during exercise with NIV (p = 0.04; r= -0.58). Furthermore, simple linear regression showed that the FEV(1) (L) affected 30% of the HF (nu) response during the exercise with NIV. CONCLUSION: NIV during exercise produced enhanced heart rate and autonomic responses in COPD-CHF patients. Additionally, COPD severity is negatively associated with a higher vagal response during exercise with NIV.