BACKGROUND Functional dyspepsia (FD) is now categorized into the epigastric pain syndrome (EPS) and the postprandial distress syndrome (PDS). However, the role of disturbed gastric emptying and sensory function for the reduction of health-related quality of life (HRQOL) has not yet been studied in EPS and PDS. METHODS A total of 300 refractory FD patients and 450 healthy blood donors (BD) were studied. BD were stratified in subjects with (BD+) and without (BD-) concomitant FD symptoms. Gastric motor and sensory function, generic and disease-specific HRQOL [physical (PCS) and mental component summary (MCS)] and affective disorders were assessed. Twenty randomly selected BD-, 50 BD+ (36 PDS, 72%), and 110 FD (95 PDS, 86.4%) patients had additional function testing. KEY RESULTS Health-related quality of life was significantly reduced in FD patients (PCS = 40.7 +/- 8.8, MCS = 39.7 +/- 11.3, both P < 0.0001) compared to BD+ (PCS = 52.0 +/- 7.6, MCS = 49.0 +/- 9.4) and BD- (PCS = 56.0 +/- 4.3, MCS = 52.8 +/- 7.2). GET (t((1/2)), min) was significantly (both P < 0.0001) longer in FD patients (143.0 +/- 7.3) compared to BD+ (101.1 +/- 6.3) and BD- (73.8 +/- 7.6). FD patients scored significantly higher for 'pain' (P < 0.0001) and 'nausea' (P = 0.023), there was no difference for 'fullness' compared to BD. Impairment of GET was not associated with HRQOL. In FD patients, an augmented symptom response to the test meal (fullness, nausea) was associated with MCS, there was no difference between FD patients with EPS or PDS. CONCLUSIONS & INFERENCES In EPS and PDS, delayed gastric empting and altered sensory function are disease markers but not directly linked to the severity of HRQOL impairment or clinical presentation of FD.