Chronic obstructive pulmonary disease (COPD) patients with chronic ventilatory failure (CVF) are more likely to develop exacerbations, which are an important determinant of health-related quality of life (HRQL). Long-term noninvasive positive-pressure ventilation (NPPV) has been proposed in addition to long-term oxygen therapy (LTOT) to treat CVF but little information is available on its effects on HRQL and resource consumption. Therefore, the current authors undertook a 2-yr multicentric, prospective, randomised, controlled trial to assess the effect of NPPV+ LTOT on: 1) severity of hypercapnia; 2) use of healthcare resources, and 3) HRQL, in comparison with LTOT alone. One hundred and twenty-two stable hypercapnic COPD patients on LTOT for > or = 6 months were consecutively enrolled. After inclusion and 1-month run-in, 90 patients were randomly assigned to NPPV+LTOT (n=43) or to LTOT alone (n=47). Arterial blood gases, hospital and intensive care unit (ICU) admissions, total hospital and ICU length of stay and HRQL were primary outcome measures; survival and drop-out rates, symptoms (dyspnoea and sleep quality) and exercise tolerance were secondary outcome measures. Follow-up was performed at 3-month intervals up to 2 yrs. Lung function, inspiratory muscle function, exercise tolerance and sleep quality score did not change over time in either group. By contrast the carbon dioxide tension in arterial blood on usual oxygen, resting dyspnoea and HRQL, as assessed by the Maugeri Foundation Respiratory Failure Questionnaire, changed differently over time in the two groups in favour of NPPV+LTOT. Hospital admissions were not different between groups during the follow-up. Nevertheless, overall hospital admissions showed a different trend to change in the NPPV+LTOT (decreasing by 45%) as compared with the LTOT group (increasing by 27%) when comparing the follow-up with the follow-back periods. ICU stay decreased over time by 75% and 20% in the NPPV+LTOT and LTOT groups, respectively. Survival was similar. Compared with long-term oxygen therapy alone, the addition of noninvasive positive-pressure ventilation to long-term oxygen therapy in stable chronic obstructive pulmonary disease patients with chronic ventilatory failure: 1) slightly decreased the trend to carbon dioxide retention in patients receiving oxygen at home and 2) improved dyspnoea and health-related quality of life. The results of this study show some significant benefits with the use of nocturnal, home noninvasive positive-pressure ventilation in patients with chronic ventilatory failure due to advanced chronic obstructive pulmonary disease patients. Further work is required to evaluate the effect of noninvasive positive-pressure ventilation on reducing the frequency and severity of chronic obstructive pulmonary disease exacerbation.