Data on the impact of functional dyspepsia on health-related quality of life in the general adult population are scarce. To explore the impact of functional dyspepsia applying the Rome III definition on health-related quality of life in the general population. A random sample of an adult Swedish population (n=1001, The Kalixanda study) was invited to undergo an oesophagogastroduodenoscopy. An extended abdominal symptom questionnaire and Short Form-36 (SF-36) questionnaire, which includes eight domains measuring physical, mental and social aspects of quality of life, were completed at the clinic visit just before oesophagogastroduodenoscopy. Two hundred and two (20%) individuals reported uninvestigated dyspepsia (UID), 157 (16%) functional dyspepsia (FD), 52 (5%) epigastric pain syndrome (EPS) and 122 (12%) postprandial distress syndrome (PDS). UID, FD and PDS had a clinically meaningful (a ≥ 5 point) and statistically significant impact (P<0.05) on health-related quality of life in all SF-36 domains except for Role Emotional. EPS had a significant impact on Bodily Pain and Vitality. Overlap of FD with irritable bowel syndrome (IBS) had a significant impact on Bodily Pain (P=0.002) and General Health (P=0.02) while FD overlap with gastro-oesophageal reflux symptoms (GERS) had a significant impact on Bodily Pain (P=0.02) compared with FD without any overlap with IBS or GERS. Functional dyspepsia impacts all main domains describing physical, mental and social aspects of health-related quality of life in the general population. Overlap of functional dyspepsia with irritable bowel syndrome or gastro-oesophageal reflux symptoms impacts the domain related to bodily pain. © 2011 Blackwell Publishing Ltd.