Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. The panel found varying quality and availability of evidence and made the following judgments: ) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, ) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, ) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, ) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and ) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement). These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.