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The effect of anemia on patients with chronic obstructive pulmonary disease (COPD) requiring invasive mechanical ventilation for acute respiratory failure is unknown.To examine the association between anemia (hemoglobin <12 g/dL) and 90-day and overall mortality in patients with COPD having acute respiratory failure requiring invasive mechanical ventilation.Retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between October 2007 and December 2012 with a diagnosis of COPD and requiring invasive mechanical ventilation for acute respiratory failure of any cause.We identified 1107 patients with COPD who required invasive mechanical ventilation for acute respiratory failure. Mean age was 64.2 ± 12.7 years; 563 (50.9%) were females. The mean Acute Physiology and Chronic Health Evaluation III score at ICU admission was 80.5 ± 29.3. The median duration of mechanical ventilation was 35.7 hours (interquartile range: 20.0-54.0). In all, 885 (79.9%) patients were anemic (Hb < 12g/dL) on ICU admission, and 312 patients (28.2%) received blood transfusion during their ICU stay. A total of 351 inhospital deaths were recorded, the majority (n = 320) occurring in the ICU. The 90-day mortality, though lower in the nonanemic patients compared to the patients with anemia, was not statistically significant (35.6% vs 44.9%; hazard ratio [HR] [95% confidence interval; CI] = 1.16 [0.91 -1.48], P = .22). The overall mortality was lower in the nonanemic patients compared to patients with anemia (HR [95% CI] = 0.68 [0.55-0.83], P < .001). There was a 5% decrease in risk of death for every unit increase in hemoglobin (P = .01). There was no difference in terms of both 90-day and overall mortality in patients who received blood transfusions compared to patients who did not receive any transfusion.Critically ill patients with COPD requiring invasive mechanical ventilation for acute respiratory failure without anemia on admission had a better overall survival when compared to those with anemia. No difference was noted in the 90-day mortality. Further studies are needed to determine the impact of the trajectory of hemoglobin on mortality.