The recently published evidence-based British Thoracic Society Guidelines for Home Oxygen in Adults (BTS Home Oxygen Guidelines) are heavily supported by two randomized control trials. With regard to LDO with NC use in chronically hypoxemic (CH) patients with COPD, the Nocturnal Oxygen Therapy Trial (NOTT) evaluated nocturnal (12 ± 2.5 h/d) vs continuous (17 ± 4.8 h/d) use; the Medical Research Council (MRC) study compared 15 h/d with no supplemental oxygen in CH control patients with COPD. The two investigations collectively support BTS Home Oxygen Guidelines’ evidence that stable CH patients with COPD (resting Pao2< 55 mm Hg) have improved life expectancy when treated with long-term oxygen therapy (LTOT) for > 15 h/d (evidence level 1+). Use in this group was also recommended because of improved pulmonary hemodynamics (grade A). Stable patients with COPD who have a resting Pao2< 60 mm Hg with cor pulmonale, polycythemia, or pulmonary hypertension have improved outcomes with LTOT (evidence level 1+). Use of 24 h of oxygen therapy offers additional survival benefit compared with shorter durations (12-15 h) but can contribute to higher Paco2 levels (evidence level 1-). LTOT in hypercapnic patients with COPD does not lead to increased morbidity, mortality, or healthcare utilization (evidence level 1+). For CH patients with COPD it was recommended that LTOT be initiated at a flow rate of 1 L/min and titrated up in 1-L/min increments until an oxygen saturation by pulse oximetry (Spo2) > 90% and an arterial blood gas confirming a target Pao2> 60 mm Hg at rest are achieved (grade B). An upper limit for Pao2 was not identified in the MRC study nor recommended in the BTS Home Oxygen Guidelines. However, arterial blood gas assessment was periodically done throughout the NOTT study, and LDO was adjusted to maintain a Pao2 of 60 to 80 mm Hg. With regard to OT, the BTS Home Oxygen Guidelines acknowledge the MRC findings. The MRC authors concluded that “[t]here was no evidence of oxygen toxicity resulting from treatment, either in the few post mortem examinations available or in physiological evidence of widening of the alveolar to arterial oxygen tension gradient.” Furthermore, the MRC results showed that compared with CH control patients with COPD, there was no increase in hospital days or days spent away from work, and no increased mortality before 500 days in the LTOT group. These findings do not support OT as a result of LDO. After comprehensive review and grading of the medical literature, the BTS Home Oxygen Guidelines presented neither evidence nor recommendations regarding the risk of OT with the use of LDO in CH patients with COPD. Furthermore, as evidence was low (evidence level 4) for LTOT in patients without COPD (cystic fibrosis, interstitial lung disease, pulmonary hypertension, advanced cardiac failure, and neuromuscular or chest wall disorders), recommendations for LTOT were extrapolated from CH COPD evidence. Of interest, in the MRC study 52% of patients in the combined groups were cigarette smokers (reduced to only 44% at study’s end). Although cigarette smoking produces reactive oxygen species and plays a major role in the pathogenesis of COPD, the BTS Home Oxygen Guidelines reported that evidence was insufficient to determine adverse clinical outcomes related to the effect of continued smoking in patients undergoing LTOT who were receiving LDO compared with never smokers (evidence level 2+).