Objective: To explore the therapeutic effect and clinical safety of modified Dingchuan Decoction combined with NPPV in the treatment of chronic obstructive pulmonary disease (COPD) complicated with respiratory failure (RF). Method: 86 patients with AECOPD combined with RF who were treated in our hospital from January 2024 to December 2025 were selected as the research subjects. The patients were divided into the control group and the study group by random number table method, with 43 cases in each group. The control group was treated with simple non-invasive positive pressure ventilation. The research group was treated with modified Dingchuan Decoction on the basis of the control group. The TCM syndrome scores, arterial blood gas indicators [arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2)], pulmonary function [forced expiratory volume in one second (FEV1), measured forced vital capacity (FVC), and FEVl /FVC], adverse reactions and therapeutic effects of the two groups were analyzed and compared. Result: The total effective rate of clinical treatment in the study group was significantly higher than that in the control group (P < 0.05). At 2 weeks of treatment, the TCM syndrome scores of both groups were significantly lower than those before treatment, and the TCM syndrome score of the study group was significantly lower than that of the control group (P < 0.05). At 2 weeks of treatment, PaO2 in both groups was significantly increased compared with that before treatment, and PaCO2 was significantly decreased compared with that before treatment. Moreover, the improvement amplitudes of PaO2 and PaCO2 in the observation group were significantly greater than those in the control group (P < 0.05). At 2 weeks of treatment, the lung functions of FEV1, FVC, and FEVl/FVC in both groups were significantly improved compared with those before treatment, and the lung functions of the study group were significantly higher than those of the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups during the treatment period (P > 0.05). Conclusion: Modified Dingchuan Decoction combined with NPPV in the treatment of COPD complicated with RF can improve clinical efficacy, alleviate TCM syndromes, enhance arterial blood gas indicators and lung function, and has good safety.