Objective To analyze the effect and compliance of systematic nursing intervention in patients with reflux esophagitis. Methods: 80 patients with reflux esophagitis admitted to our hospital from April 2020 to April 2022 were selected and randomly divided into two groups with 40 patients in each group. Routine nursing was used in the control group, and systematic nursing intervention was used in the research group. The effect and compliance of the two groups were compared. Results: After intervention, SAS and SDS in the study group were lower than those in the control group, with a statistically significant difference (P<0.05); After intervention, the scores of physical health, social relationship, mental health and surrounding environment of patients in the study group were higher than those in the control group, and the differences were statistically significant (P<0.05); The clinical compliance rate of the study group was higher than that of the control group, and the difference was statistically significant (P<0.05); The nursing satisfaction of the study group was higher than that of the control group, and the difference was statistically significant (P<0.05). Conclusion: Applying systematic nursing intervention to patients with reflux esophagitis can eliminate negative mentality, improve quality of life and clinical compliance, and effectively improve their nursing satisfaction.