Background: To evaluate the association of elevated blood glucose with the risk of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Methods: Totally 526 consecutive patients with COPD recruited between Jan. 2018 and July 2019 were included in this study. Based on the American Diabetes Association's Standards of Care, these patients were divided into three groups according to HbA1c level: low HbA1c level (HbA1c <5.7%, n=204), moderate HbA1c level (HbA1c 5.7-6.4%, n=165), and high HbA1c level (HbA1c ≥6.5%, n=157). All subjects were followed up for 18 months. Multivariate Cox regression analysis was used to evaluate the predicting value of HbA1c for the time of the next COPD severe exacerbation. Results: Totally 141 (26.8%) patients in the study had at least 1 severe exacerbation. The proportion of patients suffering from at least 1 severe exacerbation was significantly higher (P<0.01) for patients with high (36.3%) and moderate HbA1c levels (25.5%) compared to those with low HbA1c levels (20.6%). Multivariate Cox regression analysis indicated that high (HR=2.74, 95% CI: 1.70-4.41; P<0.01) and moderate HbA1c levels (HR=2.19, 95% CI: 1.39-3.46; P<0.01) were significantly associated with a higher risk of the next severe exacerbation compared with low HbA1c level, after controlling for potential confounders including age, gender, body mass index (BMI), smoking status, disease duration of COPD, frequency of hospitalization due to acute exacerbation of COPD (AECOPD) in the past 12 months, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, COPD assessment test (CAT) score, corticosteroids use, hypertension, and cardiovascular diseases. Subgroup analyses also indicated a significant association between HbA1c levels and risk of the next severe exacerbation in different GOLD stages and diabetes status. Conclusion: Elevated blood glucose, no matter with or without diabetes, is significantly associated with a higher risk of the next severe exacerbation for patients with COPD.