Abstract：Objective To  explore the clinical efficacy of tiotropium bromide powder inhalation and spray on patients with chronic obstructive pulmonary disease （COPD）. Methods A retrospective analysis was performed on the data of 198 patients with COPD who were admitted to the hospital between May 2018 and May 2020. According to the different dosage forms of tiotropium bromide, patients were divided into the inhalation group （n=89） and the spray group （n=109）. Therapeutic effects, the score of sleep quality, the score of fatigue symptoms and the incidence rate of adverse reactions were compared between the two groups. Results After treatment, the total response rate in the spray group was significantly higher than that in the inhalation group, the difference between the two groups was statistically significant （χ2＝4.940, P＜0.05）; The scores of sleep quality and fatigue in the spray group were all lower than those of the inhalation group, the difference between the two groups was statistically significant （t＝10.582, 9.190, 8.563, 7.261, 7.376, 9.999, 21.340, 9.769, 11.569, 6.043, 7.594，all P＜0.05）; There was no significant difference in the incidence rate of adverse reactions between the two groups （χ2＝1.711, P＞0.05）. Conclusion Tiotropium bromide spray can significantly improve the sleep quality at night and fatigue symptoms of patients with COPD, and the effect is better than the powder inhalation, with high application value.