Introduction:Chronic obstructive pulmonary disease (COPD) is a global health problem resulting in significant morbidity. Acute exacerbation of COPD (AECOPD) is a severe complication associated with increased short- and long-term mortality. Identifying predictors of long-term mortality after a severe AECOPD may improve management and long-term outcome of this disease. Materials and methods:A two-year prospective cohort study was undertaken in an academical medical center between 2016 and 2018. Patients with severe AECOPD who required non-invasive ventilation (NIV) were included. Baseline characteristics at inclusion, comorbidities (kidney dysfunction, left heart disease, diabetes), number of prior episodes of AECOPD and indication for long-term oxygen therapy (LTOT) or non-invasive ventilation (LTNIV) were recorded. Patients were monitored for a two-year period after initial admission. Outcomes were six-month, one-year and two-year mortality, irrespective of cause. Outcomes:51 patients (31 male, mean age 68.1) were included in the study. Mortality rates at six months, one year and two years were 20, 26 and 36%, respectively. Patients receiving LTOT and LTNIV at discharge had lower mortality at two years versus patients with no indication for LTOT and LTNIV at discharge. Absence of LTOT increased six-month mortality (OR .2, 95% CI, .04 to .90) and one-year mortality (p<.05). FEV1 and BMI were also correlated with long-term mortality in univariate analysis, p<.05. Age, number of prior episodes of AECOPD or the presence of comorbidities had no influence on long-term mortality. Conclusion:After an episode of severe AECOPD, LTOT is associated with lower long-term mortality when compared to patients with no severe hypoxemia at discharge. A decreased lung function and body mass index increase long-term mortality.