Jiarui Zhang,1,* Yichun Qin,2,* Chen Zhou,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Hui-Guo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Adila Aili,1 Lige Peng,1 Yu Liu,1 Jiaqi Pu,1 Qun Yi,1,13,* Haixia Zhou1,* 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiujiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China; 13Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haixia Zhou; Qun Yi, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37#, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cn; yiqun925@126.comBackground: High blood urea nitrogen (BUN) is observed in a subset of patients with acute exacerbation of COPD (AECOPD) and may be linked to clinical outcome, but findings from previous studies have been inconsistent.Methods: We performed a retrospective analysis of patients prospectively enrolled in the MAGNET AECOPD Registry study (ChiCTR2100044625). Receiver operating characteristic (ROC) was used to determine the level of BUN that discriminated survivors and non-survivors. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the impact of BUN on adverse outcomes.Results: Overall, 13,431 consecutive inpatients with AECOPD were included in this study, of whom 173 died, with the mortality of 1.29%. The non-survivors had higher levels of BUN compared with the survivors [9.5 (6.8– 15.3) vs 5.6 (4.3– 7.5) mmol/L, P < 0.001]. ROC curve analysis showed that the optimal cutoff of BUN level was 7.30 mmol/L for in-hospital mortality (AUC: 0.782; 95% CI: 0.748– 0.816; P < 0.001). After multivariate analysis, BUN level ≥ 7.3 mmol/L was an independent risk factor for in-hospital mortality (HR = 2.099; 95% CI: 1.378– 3.197, P = 0.001), also for invasive mechanical ventilation (HR = 1.540; 95% CI: 1.199– 1.977, P = 0.001) and intensive care unit admission (HR = 1.344; 95% CI: 1.117– 1.617, P = 0.002). Other independent prognostic factors for in-hospital mortality including age, renal dysfunction, heart failure, diastolic blood pressure, pulse rate, PaCO2 and D-dimer.Conclusion: BUN is an independent risk factor for in-hospital mortality in inpatients with AECOPD and may be used to identify serious (or severe) patients and guide the management of AECOPD.Clinical Trial Registration: MAGNET AECOPD; Chinese Clinical Trail Registry NO.: ChiCTR2100044625; Registered March 2021, URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: AECOPD, inpatients, blood urea nitrogen, mortality, adverse outcomes