To apply the concept of evidence-based nursing in the practice of inhalation therapy for patients with chronic obstructive pulmonary disease (COPD) complicated respiratory failure, introduce the application method of self-made anti-carbon dioxide retention atomizer, and to observe the application effect. Methods Patients with COPD combine respiratory failure admitted to the respiratory department of Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to April 2019 were enrolled. All patients received atomization inhalation therapy in addition to anti-infection and spasmolysis. By using self-made carbon dioxide retention atomizer time node, 40 patients in the prospective study using home-made carbon dioxide retention atomizer inhalation therapy from November 2018 to April 2019 were enrolled as observation group. Through evidence-based nursing strategy, the related literature at home and abroad was retrieved, to find the clinical evidence, formulation and implementation of care plan. Forty patients who received inhalation therapy with normal mask atomizer from May to October in 2018 were enrolled as the control group in the retrospective analysis. The peripheral arterial blood gas analysis indexes [pH value, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2)], the disappearance of pulmonary asthma at 5 minutes before atomization inhalation and 20 minutes after atomization inhalation, and the patient's cooperation in treatment were compared between the two groups. Results All patients were included in the final analysis. There was no significant difference in blood gas analysis indexes between the two groups. After 20 minutes of atomization inhalation, the pH value, PaO2 and PaCO2 of the two groups were improved, and the improvement was more obvious in the observation group [pH value: 7.32±0.35 vs. 7.25±1.25, PaO2 (mmHg, 1 mmHg = 0.133 kPa) :61.50±1.55 vs. 59.50±1.05, PaCO2 (mmHg) : 43.25±1.65 vs. 49.05±1.75, all P < 0.05]. The lung asthma in the two groups was significantly improved with 20 minutes of atomization inhalation as compared with that before atomization, and the improvement of lung asthma in the observation group was significantly better than that in the control group (asthma score: 0.91±0.29 vs. 1.65±0.35, P < 0.05). The good coordination rate of the observation group was significantly higher than that of the control group [90% (36/40) vs. 70% (28/40), χ2 = 3.828, P = 0.048]. Conclusion Compared with the inhalation treatment with ordinary mask nebulizer, inhalation treatment with self-made anti-carbon dioxide retention atomizer for COPD patients with respiratory failure can reduce carbon dioxide retention, significantly improve respiratory failure symptoms and improve compliance.