<p>The study aimed to observe the airway mucus plugs in patients with stable chronic obstructive pulmonary disease (COPD) versus those with acute exacerbation of COPD(AECOPD), and examine the clinical characteristics and prognosis in stable COPD and AECOPD with mucus plugs detected by computed tomography (CT). This prospective study enrolling patients registered in the RealDTC study from July 1, 2017 and June 30, 2023. Mucus plugs were visually-identified on CT. The symptom change, pulmonary function change, readmission, exacerbation and all-cause mortality were observed during follow up. The study enrolled 2764 COPD patients, of whom 848(30.8%) exhibited mucus plugs. The prevalence of mucus plugs in AECOPD was higher than stable COPD (45.5% versus 29.4%). Mucus plugs were associated with older age, biofuel exposure, higher CAT score, lower FEV1%predicted, lower LAA_−950HU% and higher WA%. Besides, mucus plugs increased risk of moderate-to-severe exacerbation during 1-year and 2-year follow-up, and death during total visit than those without mucus plugs both in stable COPD and AECOPD. Furthermore, mucus plugs were related to symptom deterioration, and decline in pre-and post-BD FEV1, pre-BD FEV1% and post-BD FEV1/FVC in stable COPD. In AECOPD, the presence of mucus plugs was associated with the increased length of hospital stay and higher total costs during hospitalization, as well as the escalated risk of readmission. The prevalence of airway mucus plugs in AECOPD was higher than stable COPD. Mucus plugs are related to biomass exposure, worse pulmonary function, more severe symptom, less emphysema and greater airway wall thickness. Moreover, mucus plugs may be related the elevated risk of future exacerbations and mortality. They were also associated with less improvement in pulmonary function and symptoms in stable COPD, and prolonged hospital stays, higher costs and elevated risk of readmission in AECOPD.</p>