Patients with ventilatory failure due to chronic obstructive pulmonary disease (COPD) are increasingly managed with long-term non-invasive positive pressure ventilation (NIPPV) and this may improve survival. NIPPV can frequently be interrupted but there are few data detailing the short-term effects and none on the longer-term consequences of treatment withdrawal. Ten patients withdrew from NIPPV for 1 week and were randomised to restart NIPPV or to continued withdrawal for up to 6 months. Outcomes assessed included daytime blood gases, nocturnal ventilation, lung function, exercise capacity and health status. After 1 week of withdrawal PaO(2), PaCO(2), nocturnal oximetry, lung function and exercise capacity did not change, but mean nocturnal transcutaneous CO(2) (6.3 (1) vs. 7.6 (1.1) kPa p = 0.04) and daytime blood gas bicarbonate (30.3 (4.5) vs. 31.2 (3.9) mmol/L p = 0.04) rose. During a 6-month period of withdrawal of nocturnal NIPPV, daytime PaCO(2) (6 (1.1) vs. 7.5 (1.3) kPa p = 0.002) increased and health status (total St George's Respiratory Questionnaire score 55.5 (6.3) vs. 65.6 (10) p = 0.006) worsened. Three out of five patients met a priori criteria to restart NIPPV in the continued withdrawal group. Short interruptions to domiciliary NIPPV used to manage chronic ventilatory failure as a consequence of COPD do not cause a rapid clinical deterioration but nocturnal ventilation worsens and daytime bicarbonate levels increase following 1 week's cessation. Thereafter, daytime PaCO(2) rises and health status worsens, supporting the role of long-term NIPPV in the management of such patients.