Abstract: Objective To compare the clinical effectiveness and safety of different doses of azithromycin combined with N-acetylcysteine in the treatment of chronic obstructive pulmonary disease (COPD) at remission stage. Methods Retrospective analysis was performed using clinical data from COPD patients at remission stage who were divided into the two groups: a routine therapy (control) group (n=40) and a N-acetylcysteine combined with azithromycin (observation) group (n=96). Patients in the observation group were administered with N-acetylcysteine and azithromycin in addition to routine treatment. According to the dosage of azithromycin, the observation group was subdivided into three groups: group A (n=28, 0.5 g/d), group B (n=39, 0.25 g/d) and group C (n=29, 0.125 g/d). All groups were treated for six months. The four groups were compared for pulmonary function indexes, related serum inflammatory factors and the times of COPD acute attack before and after treatment. The adverse reactions of each group were recorded during treatment. Results Before treatment, there was no significant difference in pulmonary function, serum inflammatory factors and the number of COPD acute attack among the four groups (P>0.05). After treatment, the pulmonary function indexes and serum inflammatory factors in all groups were significantly improved, compared with those before treatment (P<0.05), where the observation group showed significantly better condition than the control group (P<0.05). For the observation group, group A and group B were better than group C (P<0.05). After treatment, all the four groups presented a remarkably reduced number of COPD acute attack, compared with those before treatment, but there was no significant difference among the four groups (P>0.05). Conclusions N-acetylcysteine can be used in combination with 0.25 g/d azithromycin to treat COPD patients at remission stage, with good clinical effectiveness and safety.