〔Abstract〕 Objective To investigate the effect of moxifloxacin sequential therapy on the positive rate of next-generation sequencing (NGS) and clinical indicators in elderly patients with bacterial pneumonia. Methods A total of 98 elderly patients with bacterial pneumonia treated in the Affiliated Hospital of Putian University from January 2020 to January 2022 were retrospectively analyzed. According to the treatment regimen, they were divided into group A and group B, with 49 cases in each group. Patients in group A were treated with cephalosporins, and patients in group B were treated with moxifloxacin. The positive rate of NGS before and after treatment were compared between the two groups, and the changes of clinical indicators before and after treatment were observed in the two groups.Results The disappearance time of cough and moist rales, the recovery time of white blood cells and body temperature in group B were shorter than those in group A, and the differences were statistically significant (P < 0.05). After treatment, the forced expiratory volume in the first second/forced vital capacity (FEV1%), maximum mid-expiratory flow (MMEF) and maximum ventilatory volume (MVV) of the two groups were increased in different degrees, and FEV1%, MMEF and MVV of the group B were higher than those of the group A, and the differences were statistically significant (P < 0.05). After treatment, the serum levels of hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and procalcitonin (PCT) in two groups decreased to varying degrees, and the serum levels of hs-CRP, TNF-α and PCT in group B were lower than those in the group A, and the differences were statistically significant (P < 0.05). After treatment, the positive rate of NGS in group B was 4.08 % (2/39), which was lower than 24.49 % (12/39) in group B, and the difference was statistically significant (P < 0.05). Conclusion Moxifloxacin is more effective than cephalosporins in the treatment of bacterial pneumonia in the elderly, and it can kill pathogenic bacteria more effectively.