Background Previous work indicated that psychosocial factors (depression and somatization) are more strongly associated with symptom severity and weight loss in functional dyspepsia (FD) than gastric sensorimotor function. However, there is conflicting evidence regarding the association of these etiopathogenetic factors with Rome III symptom-based subgroups in FD [epigastric pain syndrome (EPS), postprandial distress syndrome (PDS)]. We aimed to test whether gastric sensitivity and emptying, depression, and somatization are differentially associated with empirically derived functional gastroduodenal disorders (FGD) symptom factors in one comprehensive model. Methods In 259 tertiary care FD patients, we studied gastric sensorimotor function with barostat and gastric emptying breath test. Depression, somatization, and FGD symptoms were measured using self-report questionnaires. Confirmatory factor analysis (CFA) on 7 FGD symptoms was used to determine the fit of a latent variable structure based on Rome III symptom-based subgroups. Structural equation modeling (SEM) was used to test the putative relationships of the symptom factors with gastric sensorimotor function, depression, and somatization. Key Results The results of the CFA show a good fit [Cmin/DF=1.54, CFI(comparative fit index)=0.97] for the three-factor solution based on Rome III subgroups. The SEM also fitted the data well (Cmin/DF=1.24, CFI=0.98) and demonstrated that gastric sensitivity and depression are associated with PDS and nausea and vomiting. Gastric emptying is uniquely associated with EPS and somatization is strongly associated with all three symptom factors. Conclusions & Inferences Confirmatory factor analysis confirms the existence of three FGD symptom factors, corresponding to Rome III symptom-based subgroups. The SEM results suggest that different psychobiological mechanisms may play a role in these subgroups.