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Purpose: To investigate the effect of application of tiotropium bromide and N-acetylcysteine in combination with respiratory training on the treatment of patients with chronic obstructive pulmonary disease (COPD), and the effect of the combined treatment on pulmonary function, tolerance of physical activity, and quality of life. Methods: One hundred COPD patients admitted to The First People's Hospital of Guiyang (February 2019 - March 2021) were randomly and equally assigned to groups X and Y. Patients in Y were given tiotropium bromide in combination with N-acetylcysteine, while group X was treated with respiratory training, in addition to the treatment regimen in Y. Treatment efficacy, incidence of adverse reactions, pulmonary function indices, activity tolerance, quality of life (QLI) score, activities of daily living (ADL) score, and incidence of COPD at 2 weeks, 1 month and 2 months after treatment were determined, and compared between the two groups. Results: Relative to group Y, group X had significantly higher treatment efficacy, QLI score and ADL score (p < 0.05). Furthermore, group X also had better pulmonary function indices and activity tolerance, lower incidence of adverse reactions, and lower COPD incidence at 2 weeks, 1 month and 2 months after treatment (p < 0.05). Conclusion: Tiotropium bromide and N-acetylcysteine in combination with respiratory training enhanced therapeutic effect, pulmonary function, activity tolerance and quality of life of COPD patients. [ABSTRACT FROM AUTHOR]