Gastroesophageal reflux disease (GERD), functional dyspepsia (FD), and irritable bowel syndrome (IBS) are common, and have negative impacts on health-related quality of life (HR-QOL). Several studies demonstrated a significant overlap between two of these three diseases. The purpose of this study was to examine the prevalence of GERD, FD, and IBS, their overlap rates, and HR-QOL for each disease and each overlap compared with healthy controls in the Japanese general population. We performed a cross-sectional study of Japanese workers who visited a clinic for a routine health check-up, and asked them to fill out a self-report questionnaire. Prevalence and overlap rate of GERD defined as heartburn and/or acid regurgitation at least weekly, FD and IBS based on Rome III criteria, and HR-QOL by SF-8 were examined. Of the 2680 eligible subjects, 207 (7.7%) were diagnosed as having GERD, 269 (10.0%) as FD, and 381 (14.2%) as IBS. Overlaps were found in 46.9% in GERD, 47.6% in FD, and 34.4% in IBS. Prevalence of overlaps in subjects with IBS was significantly lower compared with those among GERD or FD. Sufferers from GERD, FD, or IBS reported significantly poorer HR-QOL across all domains compared with controls. Overlaps significantly worsened HR-QOL in most domains except in the 'role emotional' domain. HR-QOL was particularly poor in the physical component summary for overlapping GERD and in the mental component summary for overlapping IBS. Overlaps among GERD, FD and IBS were common and worsened HR-QOL in Japanese general population.