OBJECTIVES: Extracorporeal life support, including venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB), triggers a pronounced inflammatory response and has been linked to postoperative liver dysfunction. Such dysfunction may negatively affect clinical outcomes after lung transplantation. Given that double-lung transplantation increasingly involves venoarterial ECMO, this work was designed to analyze the incidence of liver injury post-transplant and its impact on outcomes, specifically duration of intensive care unit (ICU) stay and 1-year mortality. DESIGN: Retrospective analysis. SETTING: Single university hospital. INTERVENTIONS: None. PARTICIPANTS: Data from 1,350 consecutive patients who underwent lung transplantation between January 2009 and April 2023 were analyzed. MEASUREMENTS AND MAIN RESULTS: Hepatic injury occurring within the first 12 postoperative days was classified as hypoxic liver dysfunction, drug-induced liver injury, or cholestasis. The corresponding incidences were 4%, 23%, and 52%, respectively. All were associated with an increased length of ICU stay. Owing to the multiple medications these patients receive post-transplantation, a clear distinction between drug-induced liver injury and a mild form of hypoxic liver dysfunction is difficult. However, only the latter was independently linked with increased 1-year mortality amounting to 35%. Patients who developed hypoxic liver dysfunction were more frequently operated on CPB or required prolonged ECMO support. CONCLUSION: Lung transplantation involving CPB or extended perioperative ECMO support significantly increases the risk of severe postoperative liver dysfunction associated with poorer outcomes. However, brief intraoperative ECMO deployment does not appear to carry this risk.