To observe the efficacy of mosapride combined with esomeprazole magnesium enteric-coated tablets in the treatment of elderly patients with chronic atrophic gastritis (CAG), and the influence on gastric motility and gastric mucosa prostaglandin E2 (PGE2) level.Methods A total of 146 elderly patients with CAG admitted to the hospital from January 2021 to January 2022 were selected, and divided into 2 groups by random number table method.Patients in control group took mosapride, and those in observation group took esomeprazole magnesium enteric-coated tablets on this basis.The two groups were compared in terms of gastric motility (electrogastrogram amplitudes and gastrin levels before and after the meal), gastric mucosa PGE2, inflammatory factors ［interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α)］, clinical effect, symptom disappearing time, and adverse reactions.Results The total response rate in observation group was significantly higher than that in control group (P＜0.05).The disappearance time of abdominal distension and pain in observation group was significantly shorter than that in control group (P＜0.05).After treatment, electrogastrogram amplitudes and gastrin levels before and after the meal in observation group were significantly greater/higher than those in control group (P＜0.05). After treatment, gastric mucosa PGE2 level in observation group was significantly higher than that in control group, and the levels of IL-6, IL-8 and TNF-α were significantly lower than those in control group (all P＜0.05).There was no significant difference in the total incidence of adverse reactions between the two groups (P＞0.05).Conclusion Mosapride combined with esomeprazole magnesium enteric-coated tablets can effectively improve gastric motility and gastric mucosa PGE2 level in elderly patients with CAG, relieve inflammation, and promote the disappearance of clinical symptoms, with a few adverse reactions