OBJECTIVE To assess the values of endoscopy, 24-hour esophageal pH monitoring, symptom index, 24-hour esophageal bile monitoring, and proton pump inhibitor (PPI) trail in the diagnosis of gastroesophageal reflux disease (GERD)-related noncardiac chest pain (NCCP). METHODS 27 NCCP patients, selected from a consecutive sample of 255 patients who had received coronary angiography owing to chest pain, underwent upper endoscopy, and 24-hour esophageal pH and bile monitoring, then they took esomeprazole 20 mg orally twice daily for 14 days. Symptom score (SI) was used to measure the severity and frequency of chest pain before and after treatment. The patients also underwent an initial questionnaire survey including the general personal data and symptom characters, reflux diagnostic questionnaire (RDQ), self-rating anxiety scale (SAS) survey, and self-rating depression scale (SDS) survey. RESULTS If only based on erosive esophagitis and/or abnormal 24-hour esophageal pH monitoring, 9 of the 27 patients (33%) were classified as GERD-related NCCP. Otherwise, 74% (20 of the 27 patients were classified as GERD-related NCCP based on erosive esophagitis and/or abnormal 24-hour esophageal pH monitoring, or positive SI or abnormal bile monitoring. 15 of the 20 GERD patients (75%) had a significant symptom improvement on PPI compared with 14% (1/7) of non-GERD patients (P = 0. 009). The calculated sensitivity and specificity of the PPI trail was 75% and 86% respectively. The typical reflux symptoms presented more frequently among GERD patients than non-GERD patients [65% (13/20) vs 29% (2/7), P = 0.185]. There was no significant RDQ score difference between the 2 groups (10 +/- 4 vs 8 +/- 4, P = 0.411). The sensitivity and specificity of RDQ to GERD-related NCCP were 35% and 86% respectively. The SAS scores of GERD and non-GERD-related NCCP patients were both significantly higher than that of the normal controls (P = 0.008 and P = 0.011), while the SDS scores of the GERD and non-GERD-related NCCP patients were both similar to that of the normal controls (P = 0.090 and P = 0.113). CONCLUSION Combination of endoscopy, 24-hour esophageal pH monitoring, SI, and 24-hour esophageal bile monitoring helped to improve the diagnosis of GERD-related NCCP. PPI trail is the first clinical diagnostic tool in the evaluation of GERD-related NCCP.