Objective: To investigate the clinical and pulmonary function characteristics, risk of acute exacerbation, and associated correlations in moderate-to-severe stable chronic obstructive pulmonary disease (COPD) patients with inspiratory plateau on the flow-volume (F-V) curve. Methods: A total of 109 patients with moderate-to-severe stable COPD [forced expiratory volume in the first second as a percentage of predicted value (FEV₁% pred) <60% and forced vital capacity (FVC) ≥ lower limit of normal] who underwent pulmonary function tests at the First Affiliated Hospital of Nanjing Medical University from January 2022 to July 2024 were enrolled. Patients were divided into inspiratory plateau group(n=53) and non-inspiratory plateau group matched for FEV₁%pred(n=56) based on the presence or absence of inspiratory plateau. Demographic data, types of inhaled medications, acute exacerbation, chest CT findings, pulmonary function parameters, and clinical comorbidities were collected and compared between the two groups. Multivariate logistic regression identified factors associated with the F-V curve inspiratory plateau. A diagnostic model for identifying the inspiratory plateau in patients with moderate-to-severe stable COPD was constructed and calibrated using the Hosmer-Lemeshow test, and evaluated using the area under the receiver operating characteristic curve(AUC). Chi-square test was used to preliminarily explore the association between inspiratory plateau and various comorbidities in patients with moderate-to-severe stable COPD. Results: ①The difference in the proportion of pulmonary function stages between the two groups was not statistically significant (P > 0.05). ②The inspiratory plateau group exhibited significantly lower values for peak expiratory flow as a percentage of predicted value, peak inspiratory flow(PIF), total lung capacity as a percentage of predicted value, and alveolar volume as a percentage of predicted value, but significantly higher values for the ratios of peak expiratory flow (PEF) to PIF(PEF/PIF), the ratios of forced expiratory volume in the first second(FEV₁) to PEF(FEV₁/PEF), resistance at 5 Hz(R₅) as a percentage of predicted value, resistance at 20 Hz(R₂₀) as a percentage of predicted value, the difference between R₅ and R₂₀(R₅-R₂₀), and resistance of central airway(Rcentral) compared to the non-inspiratory plateau group(P < 0.05). ③No statistically significant difference was found in the rate of acute exacerbation between groups(P > 0.05), although the inspiratory plateau group exhibited a higher acute exacerbation rate and slightly higher hospitalization rate. ④A diagnostic model was constructed using PIF, PEF/PIF, FEV₁/PEF and Rcentral. The optimal thresholds for the influencing factors within this model were PIF≤3.91 L/s, PEF/PIF≥0.830, FEV₁/PEF≥0.369 s and Rcentral≥1.905 cmH₂O/(L·s). This model demonstrated strong discriminatory power with an AUC of 0.945. The Hosmer-Lemeshow goodness-of-fit test yielded a P-value of 0.957, indicating good model calibration. ⑤Compared with the non-inspiratory plateau group, the inspiratory plateau group had higher prevalences of upper airway stenosis and central pulmonary malignancy, and the differences were statistically significant (P < 0.05). Conclusion: Moderate-to-severe stable COPD patients with inspiratory plateau in the F-V curve frequently exhibit increased overall airway resistance, suggesting potential upper airway and surrounding disorders. Therefore, the presence of an inspiratory plateau should be carefully evaluated in pulmonary function reports of moderate-to-severe stable COPD. A multi-parameter model incorporating PIF, PEF/PIF, FEV₁/PEF, and Rcentral may be utilized for identification, facilitating early detection of comorbidities in COPD patients.