BACKGROUND: Patients with gastroesophageal reflux disease (GERD) frequently report symptoms like dyspepsia or/and irritable bowel syndrome (IBS). The aim of the study was to investigate the impact of symptom overlap on GERD symptom burden. We also investigate whether GERD overlapping dyspepsia or/and IBS would have different clinical and psychological features as compared with GERD alone. METHODS: A total of 2752 subjects were screened from a health check-up population. We compared the clinical and psychological factors among subjects with GERD alone and with overlap of two or all three diseases. All participants underwent an evaluation with questionnaires including Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory before receiving endoscopic exam. RESULTS: Among the GERD population, we identified 26 with IBS (GERD-IBS), 60 with dyspepsia (GERD-D), and 25 subjects with overlap of all three conditions (GERD-D-IBS). GERD-D and GERD-D-IBS subjects had more severe GERD symptoms as compared subjects with GERD alone (p < 0.001). Subjects with overlapping dyspepsia or/and IBS showed a significant increase in the severity of depression and poorer sleep quality than subjects with GERD alone. Notably, anxiety scores did not differ significantly between subjects with overlapping diseases and GERD alone. CONCLUSION: Our study demonstrates that disease overlap in GERD population is associated with greater symptom burden, higher depression and poorer sleep quality, but not with anxiety. This study highlights the importance of identifying overlapping conditions as a therapeutic strategy for better management of GERD.