Considerable risk of burn injury exists for those patients on home oxygen therapy (HOT) who continue to smoke. In this study, the authors sought to establish the national incidence of burns incurred while smoking on HOT and to determine the resource utilization and sequelae of these injuries. A retrospective review of the American Burn Association's National Burn Repository was conducted to identify patients burned while on HOT during the years 2002 to 2011. Duplicate entries, as well as records of follow-up visits and readmissions, were removed. Univariate analysis was used to compare the differences between patients sustaining burn injuries related to HOT and patients with other mechanisms of injury. Multivariate analysis provided odds ratios for mortality controlling for all significant variables. The frequency of burns sustained on HOT significantly increased during the 10-year period reviewed and were associated with increased comorbidities and certain complications. Compared with non-HOT injuries, HOT injuries had higher incidence of inhalation injury and mortality. Inhalation injury was the strongest predictor of mortality in HOT burn injuries. The likelihood of poor prognosis was even more pronounced in patients who required intubation. Smoking was responsible for 83% of the HOT burn injuries described here. Therefore, smoking cessation counseling and treatment should be mandatory in all patients prescribed HOT.