Objective To evaluate the clinical efficacy of flupentixol melitracen joint esomeprazole, mosapride in the treatment of refractory gastroesophageal reflux disease.Methods 80 patients with refractory gastroe-sophageal reflux disease were randomly divided into control group and observation group,40 cases in each group.Two groups of patients were given oral esomeprazole and mosapride treatment,the observation group was treated with flu-pentixol melitracen on the basis of control group.4 weeks for a course of treatment,patients were treated for 2 courses. The clinical efficacy of the two groups,the depression and anxiety RDQ score before and after treatment,the adverse reactions were recorded.Results The total effective rate of the observation group was 82.50%,which was signifi-cantly higher than 70.00% of the control group,the difference was statistically significant (χ2 =3.660,P <0.05). Before treatment,SAS,SDS score and RDQ level between the two groups had no significant difference (all P >0.05). After treatment,the RDQ in symptom score and frequency integrator of the control group were (8.12 ±0.89)points, (7.70 ±1.00)points,compared with before treatment,the differences were significant (t =4.70,6.37,all P <0.05),and those of the observation group were (5.21 ±0.45)points,(4.71 ±0.78)points,which were significantly lower than those of the control group,the differences were statistically significant (t =1.81,1.81,all P <0.05).After treatment,the SAS score and SDS score of control group were (49.12 ±5.89)points,(50.30 ±6.00)points,com-pared with before treatment,the differences were significant (t =1.81,1.81,all P <0.05),and those of the observa-tion group were (41.21 ±5.45),(43.71 ±5.78),which were significantly lower than the control group (t =2.30, 1.91,all P <0.05).During the treatment,the adverse events in the two groups were similar,no serious adverse reac-tions were observed.Conclusion Flupentixol melitracen joint esomeprazole,mosapride in the treatment of refractory gastroesophageal reflux disease has significant clinical effect,can effectively improve the clinical symptoms of depres-sion and anxiety scores,and without significant adverse reactions,it is worthy of clinical application.