OBJECTIVES: Endoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool for gastroesophageal reflux disease (GERD). EPSIS has been developed to evaluate lower esophageal sphincter function by monitoring the intragastric pressure (IGP) while insufflating the stomach during gastroscopy. Based on previous data, EPSIS could diagnose GERD with good accuracy by assessing IGP waveform pattern. This study aimed to further characterize the waveform to improve the diagnostic yield of EPSIS. METHODS: We conducted a retrospective analysis of patients with typical GERD symptoms who underwent both EPSIS and 24-hour impedance-pH monitoring (MII-pH) at a single tertiary referral center from October 2018 to May 2020. EPSIS was performed by using a through-the-scope catheter connected to the pressure measuring system (TR-W550, TR-TeH08, AP-C35; Keyence, Osaka, Japan) to monitor IGP. Abnormal acid reflux was defined as acid exposure time (AET) over 6.0%. Pressure waveform was characterized as follows: a) Basal IGP, b) Maximum IGP, c) Pressure difference, d) Gradient of the waveform. RESULTS: A total of 57 patients with GERD symptoms were analyzed. Twenty-one patients presented abnormal AET on MII-pH. Among EPSIS parameters, pressure difference during insufflation correlated with AET (ρ= -0.66, p<0.001) and showed the best diagnostic accuracy for AET with the cut-off value of 8.0 mmHg (AUC 0.87). The gradient of EPSIS waveform also revealed good diagnostic accuracy for abnormal AET with the cut-off value of 0.11 mmHg/sec (AUC 0.81). CONCLUSIONS: EPSIS waveform parameters, especially pressure difference, presented high diagnostic accuracy for the presence of abnormal acid reflux.