The aims of this study were to compare the therapeutic effects of a proton pump inhibitor (PPI), rabeprazole (RPZ), and a prokinetic agent, itopride (ITO), and to investigate the role of PPI in the treatment strategy for Japanese functional dyspepsia (FD) patients. We randomly assigned 134 patients diagnosed by Rome III criteria to 4 weeks treatment with RPZ 10 mg/day ( n = 69) or ITO 150 mg/day ( n = 65). Dyspeptic symptoms were evaluated using FD scores at baseline and after 1, 2 and 4 weeks of treatment. We also divided subjects into predominantly epigastric pain syndrome (EPS) or postprandial distress syndrome (PDS), and evaluated the efficacy of RPZ and ITO respectively. RPZ showed a significant decrease in the Rate of Change (RC) in FD score within 1 week, which was maintained until after 4 weeks, with RPZ a significant effect compared with ITO at all evaluation points. In addition, RPZ showed a significant decrease in FD score in subjects with both EPS and PDS, whereas a significant decrease in the RC with ITO was only shown in those with predominant PDS. Acid-suppressive therapy with RPZ is useful for PDS as well EPS in Japanese FD patients (UMIN Clinical Trials Registry number: UMIN 000013962).