Abstract: Objective To investigate the clinical efficacy and safety of lansoprazole in the treatment of patients with gastroesophageal reflux disease. Methods A total of 180 patients with gastroesophageal reflux disease were divided into control group and observation group by blind selection method, with 90 cases in each group. Both groups were treated with mosapride. On this basis, the control group was treated with additional omeprazole, while the observation group was treated with additional lansoprazole. Before and after treatment, the scores of symptoms, esophageal mucosal lesions, clinical efficacy and adverse reactions were compared between the two groups. Results After treatment, the scores of symptoms in both groups were significantly lower than those before treatment, and the scores of symptoms such as acid regurgitation, burning feeling in stomach, reflux and non-cardiogenic chest pain in the observation group were significantly lower than those in the control group(P<0.05). After treatment, the proportions of patients with grade N and grade M esophageal mucosal lesions in the observation group were significantly higher than those in the control group, while the proportions of patients with grade A, grade B and grade C were significantly lower than those in the control group(P<0.05). The total effective rate of the observation group was significantly higher than that of the control group(P<0.05). After treatment, the total incidence rate of adverse reactions in the observation group was significantly lower than that in the control group(P<0.05). Conclusion Lansoprazole is effective and safe in the treatment of patients with gastroesophageal reflux disease, which can significantly improve the symptoms of patients and esophageal mucosal lesions.