Background The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease (GERD) on proton-pump inhibitor (PPI) therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD patients.Methods GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH+ group did not.Results Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% (52/58) of symptom-free patients and 67% (12/18) of symptom-persistent patients achieved esophageal pH normalization after therapy (P=0.030). The mean post-therapy gastric nocturnal percent time of pH ＜4.0 was significantly higher in pH+group than that in pH- group (P ＜0.001) after therapy. The multivariate regression analysis identified hiatus hernia (P＜0.001) and persistent reflux symptom (P=0.004) were two independent factors predicting the low post-therapy esophageal pH level.Conclusions Symptom elimination is not always accompanied by esophageal pH normalization, and vice verse.Esophageal pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.