Objective: To investigate the predictive diagnostic value of forced expiratory volume as a percentage of predicted value (FEV1% pred) , pro-brain natriuretic peptide (pro-BNP) and high-sensitivity C-reactive protein (hs-CRP) on respiratory failure in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: 32 patients with AECOPD complicated with respiratory failure in the People’ s Hospital of Ningdu County from June 2023 to November 2024 were included in observation group, and 32 AECOPD patients without respiratory failure in the same hospital during the same time period were regarded as control group. At admission, the levels of laboratory indicators were compared between groups, including FEV1% pred, hs-CRP and pro-BNP. Receiver operating characteristic (ROC) curve was adopted to analyze the predictive value of FEV1% pred, hs-CRP and pro-BNP on respiratory failure in AECOPD patients. Results: Univariate analysis showed that compared with patients with mild ADL grade, lymphocyte count (L)>1×109/L, FEV1% pred≥50%, pro-BNP<300 ng/L and hs-CRP<10 mg/L, patients with moderate-to-severe ADL grade, L≤1×109/L, FEV1%pred<50%, pro-BNP≥300 ng/L and hs-CRP≥10 mg/L had a higher proportion of respiratory failure (P<0.05 ). Multivariate analysis revealed that FEV1%pred<50%, pro-BNP≥300 ng/L and hs-CRP≥10 mg/L were risk factors for respiratory failure in AECOPD patients (P<0.05). ROC curve indicated that the areas under the curves (AUCs) of FEV1% pred, hs-CRP, pro-BNP and combination of three indicators in the diagnosis of respiratory failure in AECOPD patients were 0.743, 0.740, 0.716 and 0.820, the sensitivities were 71.87%, 65.62%, 65.62% and 62.50%, and the specificities were 75.00%, 90.62%, 87.50% and 93.75% respectively. The diagnostic efficiency of combination of the three indicators was higher (P<0.05). Conclusion: The FEV1% pred of AECOPD patients with respiratory failure is lower than that of patients without respiratory failure, while the levels of hs-CRP and pro-BNP are higher than those of patients without respiratory failure. The combined detection of the above indicators can be used to assist the diagnosis of respiratory failure in AECOPD patients, and it has reference significance.