A combination of multiple tests was introduced to noninvasively investigate the differences in pathophysiologies among functional dyspepsia (FD) subgroups, including postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlap.It has not been extensively evaluated whether different pathophysiologies are involved in FD subgroups.This multicenter study included 364 FD patients fulfilling Rome IV criteria and 47 healthy controls. A combined noninvasive gastric and autonomic function test was performed: The electrogastrogram and electrocardiogram were recorded simultaneously in the fasting state and after a drink test. Symptoms after drinking were recorded using visual analog scale.(1) Compared with HC, FD patients showed a decreased maximum tolerable volume (MTV) (P<0.01) and percentage of normal gastric slow waves [normal gastric slow waves (%NSW)] (P<0.01), and increased postdrinking symptoms, anxiety (P<0.01), and depression (P<0.01). The drink reduced %NSW in both FD patients and HC; however, the effect was more potent in patients. (2) The PDS and overlap groups displayed a reduced MTV (P<0.05). The overlap group exhibited a higher symptom score at 30 minutes after drinking, and higher anxiety and depression scores, and a higher sympathovagal ratio than the EPS (P<0.05 for all) and PDS (P<0.01 for all). (3) In the PDS subgroup, the MTV, postprandial sympathovagal ratio, and depression were associated with the overall dyspepsia symptom scale (DSS, P=0.034, 0.021, 0.043, respectively). No significant associations were found in the other 2 subgroups.The combination of multiple tests can detect pathophysiological abnormities in FD patients. Overall, patients with overlap symptoms display more severe pathophysiologies.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.