Objective: To analyze key factors associated with the failure of non-invasive ventilation (NIV) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) complicated by type II respiratory failure. Methods: A total of 122 patients with AECOPD and type II respiratory failure admitted to Gaoyou People’s Hospital between January 2020 and June 2023 were selected for the study. Upon admission, all patients received ECG monitoring and NIV, along with comprehensive therapies such as anti-infective treatment, antispasmodics, bronchodilators, and expectorants. NIV was provided using the S/T mode, with ventilator parameters adjusted based on the patient’s respiratory status and blood gas analysis results. Clinical data were retrospectively analyzed from electronic medical records. Results: Out of the 122 patients, 30 experienced NIV failure, accounting for 24.59%. Significant differences were observed in C-reactive protein (CRP), pH, and partial pressure of arterial carbon dioxide (PaCO₂) between patients with successful and failed NIV outcomes (P < 0.05). There were no statistically significant differences in gender, age, arterial oxygen partial pressure (PaO₂), neutrophil count (NEUT), procalcitonin (PCT), albumin (ALB), or tidal volume between the two groups (P > 0.05). Logistic regression analysis confirmed that CRP, pH, and PaCO₂ were significant risk factors for NIV failure (P < 0.05). Conclusion: CRP, pH, and PaCO₂ are independent risk factors influencing NIV failure.