Case Reports: Hepatopulmonary syndrome (HPS) is defined as a clinical triad of chronic liver disease, abnormal pulmonary gas exchange resulting in arterial hypoxemia, and evidence of intrapulmonary vascular dilations producing a right to left intrapulmonary shunt. The only definitive treatment option is liver transplantation, with an anticipated improvement and subsequent resolution of hypoxemia weeks to months following transplantation. In light of an increasing trend to transplant patients with severe HPS characterized by profound hypoxemia, practical alternatives to high flow nasal cannula (HFNC) need to be considered in order to facilitate post-transplant patient mobilization and early discharge from the hospital while treating severe hypoxemia. To this end, we describe our experience with the application of transtracheal oxygen therapy in the management of post-operative hypoxemia following OLT for severe HPS in three patients. Persistent arterial hypoxemia in the immediate post-operative period required the use of high-flow nasal cannula (HFNC) oxygen. Although allograft function steadily improved, the patients’ hypoxemia did not improve in the immediate post-operative period, and they subsequently underwent placement of a transtracheal oxygen (TTO) catheter to facilitate mobilization and weaning from HFNC. Therapy with oxygen via the TTO catheter led to early patient mobilization and discharge, and rapid weaning and eventual liberation from supplemental oxygen. To our knowledge, this is the first report of such a management technique for this unique group of patients. Our observations highlight the utility of transtracheal oxygen therapy in the management of severe HPS after liver transplantation.