Background and Objective: Elevated eosinophils in chronic obstructive pulmonary disease (COPD) are recognized as a biomarker to guide inhaled corticosteroids use, but the value of blood eosinophils in hospitalized exacerbations of COPD remains controversial. This study aimed to evaluate the accuracy of eosinophils in predicting clinical outcomes in acute exacerbation of COPD (AECOPD). Methods: We analyzed data from the acute exacerbation of chronic obstructive pulmonary disease inpatient registry (ACURE) study, which is an ongoing nationwide multicenter, observational real-world study in patients admitted for AECOPD. Data collected between January 2018 and December 2019 in 163 centers were first reviewed. The eligible patients were divided into eosinophilic and non-eosinophilic groups, according to blood eosinophil with 2% of the total leukocyte count as the threshold. Propensity score (PS) matching was performed to adjust for confounders. Results: A total of 1,566 patients (median age: 69 years; 80.3% male) were included and 42.7% had an eosinophilic AECOPD. Eosinophil count <2% was associated with the development of respiratory failure and pneumonia. After PS matching, 650 pairs in overall patients, 468 pairs in patients with smoking history and 177 pairs in patients without smoking were selected, respectively. Only in patients with smoking history, the non-eosinophilic AECOPD was associated with longer median hospital stays (9 vs. 8 days, P = 0.034), higher dosage of corticosteroid use, higher economic burden of hospitalization, and poorer response to corticosteroid therapy compared to the eosinophilic AECOPD. No significant difference was found in patients without smoking. Eosinophil levels had no relationship with the change of COPD Assessment Test scores and readmissions or death after 30 days. Conclusion: Elevated eosinophils were associated with better short-term outcomes only in patients with a smoking history. Eosinophil levels cannot be confidently used as a predictor alone for estimating prognosis.