INTRODUCTION: A nationwide chronic obstructive pulmonary disease (COPD) quality improvement programme - DrCOPD - was initiated in Denmark in 2008. We examined subsequent national and regional trends in the use of non-invasive ventilation (NIV) and trends in mortality following NIV and invasive mechanical ventilation among patients acutely admitted with a COPD exacerbation. MATERIALS AND METHODS: We did a nationwide, population-based prospective study using DrCOPD to identify all incident hospitalizations with COPD from 2008 through 2011 (n = 24,982) and to record the use of NIV during hospitalization. Date of death was retrieved from the Danish Civil Registration System. RESULTS: During follow-up, the use of NIV treatment in patients with first-time COPD hospitalization increased statistically significantly in all five Danish regions. At the national level, the use of NIV increased from 5.8% to 7.0% (adjusted for age, sex and co-morbidity, relative risk (RR): 1.21, 95% confidence interval (CI): 1.05-1.38). Concurrently, a statistically significant increase from 1.3% to 1.8% (RR: 1.36; 95% CI: 1.03-1.80) in NIV given together with invasive mechanical ventilation was observed. During the four years of follow-up, mortality remained stable with some regional variation. In-hospital mortality following NIV was also stable over time, while mortality decreased slightly in patients treated with both NIV and invasive mechanical ventilation. CONCLUSION: Use of NIV in Denmark increased after the launch of a national COPD quality programme in 2008. However, regional variation remains and no substantial improvements in mortality have been observed. Continued efforts are warranted to ensure appropriate implementation of NIV. FUNDING: The study was supported financially by University of Copenhagen and the Danish Lung Association. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (record no. 2012-41-0438), the Danish National Indicator Project, Danish Regions and the Danish Ministry of Health.