High-pressure non-invasive positive pressure ventilation (NPPV) is a new strategy targeted at maximally reducing arterial carbon dioxide. However, high inspiratory positive airway pressure (IPAP) might cause respiratory adverse events likely to diminish the benefit of NPPV. In the setting of ventilatory support, monitoring NPPV efficacy and resolving problems promptly are critical. This study assessed the treatment effect of high and low-pressure NPPV in chronic hypercapnic COPD using home ventilator with built-in software. In this pilot study, we investigated 34 patients using NPPV for 3 months. 13 patients used high-pressure ventilation and 21 patients used low-pressure ventilation. The primary outcome was daytime partial pressure of arterial blood carbon dioxide (PaCO2). There were no between-group differences in daytime PaCO2 and FEV1, but a trend favouring high-pressure NPPV was observed. Significant between-group differences were found in the transition dyspnoea index (TDI) (high-pressure, 1.69 ± 1.75, versus low-pressure, -0.04 ± 2.71, p = 0.044). No differences were found in usage time, leakage, health-related quality of life, spirometry, or 6-minute walk test. High-pressure NPPV with built-in software monitoring in patients with chronic hypercapnic COPD is associated with improvement in TDI scores and a positive trend in favour of high-pressure NPPV for improving PaCO2 is observed.