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Background: The aetiologies of chronic respiratory failure (CRF) are moving in many western countries. Obesity-Hypoventilation syndrome (OHS) has become one of the most common indications of non-invasive ventilation (NIV) with Chronic Obstructive Pulmonary Diseases (COPD). Long-Term Oxygen Therapy (LTOT) technology is the treatment plan for CRF patients in the new era. Objectives: This study aimed to assess home-based care evolution in CRF patients on LTOT (LTOT) and/or NIV from the ANTADIR observatory. Methods: A computerized database from 14 regional facilities was analysed (30% of French home-treated patients). Patient age, sex, aetiology, home respiratory devices were recorded between 2001 and 2015. Results: By the end of 2015, 12,147 CRF patients received LTOT (40%), NIV (24%), LTOT + NIV (23%), continuous positive airway pressure (CPAP; 11%) or LTOT + CPAP (3%). Between 2001 and 2015, we observed a decrease of LTOT (63–40%) in the benefit of NVI ± LTOT (25–47%). Regarding the aetiology, we note a slight decrease in obstructive disease and a significant increase in restrictive disease, mainly due to OHS. The 10-year survival was better on NIV ± LTOT than on LTOT, for overall patients and for both obstructive and restrictive patients. The 10-year survival was better on NIV ± LTOT than on LTOT (35 vs. 10%, p < 0.05). In COPD patients on LTOT, a switch from conventional to new home devices was observed. Stationary LTOT systems were less prescribed, while portable/transportable system, liquid oxygen and self-filling oxygen were increasingly prescribed. Conclusion: Our study confirmed changes in CRF aetiologies and home devices. OHS is now an important indication of NIV. Using new LTOT technologies changed home prescriptions in COPD patients.