Background <p>Many studies have been conducted on the impact of eosinophilia in chronic obstructive pulmonary disease (COPD) patients; however, there is a lack of clear data showing the relationship with the success of non-invasive ventilation (NIV) in exacerbations. This study aimed to investigate whether the eosinophilic endotype predicts the response to NIV in patients with COPD exacerbations presenting with acute respiratory failure. We also sought to determine if eosinophil cutoff values of ≥ 2% and ≥ 0.34 cells/L, previously used to define eosinophilic exacerbations, are effective in predicting NIV success.</p> Methods <p>A retrospective analysis was conducted on 1142 patients admitted to the emergency room (ER) of a tertiary chest diseases hospital for COPD exacerbation with acute respiratory failure, who received NIV. Data were obtained from the electronic data management system and ER triage. Patients were categorized into two groups: NIV success and NIV failure. NIV success was defined as discharge from the ER or admission to the ward, while NIV failure was defined as intubation, death, or admission to the intensive care unit (ICU). Differences between the groups were analyzed.</p> Results <p>Of the 1142 patients, 816 (71%) were male, with a mean age of 66 years (range: 40–80). A total of 932 (82%) patients were in the NIV success group, while 210 (18%) were in the NIV failure group. The eosinophilic endotype, defined by a cutoff of ≥ 2%, was observed in 33% of NIV success patients and 25% of NIV failure patients (<i>p</i> &lt; 0.05). An absolute eosinophil count of ≥ 0.34 cells/L was found in 13% (<i>n</i> = 120) of NIV success patients and 9% (<i>n</i> = 19) of NIV failure patients (<i>p</i> &gt; 0.05).</p> Conclusion <p>Our study suggests that NIV success in COPD exacerbation is more likely when the eosinophil percentage is ≥ 2%. This may be attributed to the fact that exacerbations in the eosinophilic endotype are generally less severe and respond better to corticosteroid therapy.</p>