〔Abstract〕 Objective To observe the efficacy and safety of azithromycin combined with teicoplanin in the treatment of outpatient lower respiratory tract infection. Methods A total of 112 patients with lower respiratory tract infection in the Seventh People's Hospital of Zhengzhou from June 2019 to May 2021 were selected and divided into a control group and an observation group according to the random number table method, with 56 cases in each group. The control group was treated with azithromycin, and the observation group was treated with teicoplanin on the basis of the control group. The clinical effects, the disappearance time of symptoms, the levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP) before and after treatment, and the incidence of adverse reactions were compared between the two groups. Results The total effective rate of the observation group was 98.21 %, higher than 78.57 % of the control group, and the difference was statistically significant (P < 0.05). The cough disappearance time, fever disappearance time and sputum disappearance time of the observation group were shorter than those of the control group, and the differences were statistically significant (P < 0.05). After treatment, the serum levels of TNF-α, IL-6 and hs-CRP in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Azithromycin combined with teicoplanin in the treatment of outpatients with lower respiratory tract infection can quickly relieve the clinical symptoms of patients, reduce the inflammatory response, and has high safety.