BACKGROUND: Early extubation is a fundamental element integrated into enhanced recovery protocols in orthotopic liver transplantation (OLT). The aim is to evaluate whether early extubation influences short- and medium-term postoperative morbidity and mortality. METHODS: A cohort of 209 patients who underwent OLT in a tertiary hospital in a period from January 2016 to December 2018 were retrospectively analyzed. Patients were divided into 2 groups: group 1: early extubation in the intensive care unit and group 2: delayed extubation. Mortality is compared between both groups in the first month and first and third year. Postoperative morbidity was also compared. RESULTS: Patients in group 1 (n = 165, 79.9%) presented, with statistical significance, lower mortality at 1 month, 1 year, and 3 years; shorter duration of admission to the critical care unit and of hospital stay; lower incidence of surgical reoperation and retransplant; lower rate of transfusion of blood products; fewer pulmonary, digestive, neurologic, cardiologic, hemodynamic, kidney, surgical, infectious, metabolic, thrombotic, vascular, and graft complications; less need for kidney replacement therapy; less refractory ascites; and greater infectious risk. However, no statistically significant differences were found in the need for hospital readmission; in biliary, endocrine, nutritional, hematologic, thrombotic, and hematologic complications; or in graft rejection. In group 1, 6.6% of patients required reintubation. In group 2, 97% of patients could be extubated during the first week; 7.8% required noninvasive mechanical ventilation type bilevel positive airway pressure and 8.1% high flow. Only 2.8% of patients required tracheotomy. CONCLUSIONS: The role of early extubation seems key to improve outcomes in OLT because it reduces the incidence of multiple complications and mortality, with low reintubation rates. It is a feasible and safe procedure.