The efficacy of S-1 for stage II–III gastric cancer after D2 gastrectomy has been shown by ACTS-GC trial. However, the survival of stage III remains unsatisfactory(the 3-year relapse-free survival (RFS) rates in stage IIIA and IIIB receiving S-1 were 68.0% and 49.8%, respectively). Therefore, further investigation of more effective treatments is urgently needed.Several trials have been reported about adjuvant S1-combined chemotherapy for stage III gastric cancer. Firstly, we reported S-1 plus three cycles of cisplatin followed by S-1 monotherapy. After amend the protocol, the regimen proved to be feasible. The 3-year RFS rate was 73.4% (IIIA 81.6%, IIIB 61.6%). The 3-year overall survival rate was 84.1% (IIIA 87.4%, IIIB 79.8%). S-1 plus four cycles of docetaxel followed by S-1 was also reported feasible; however, the 3-year RFS was 50.3% (IIIA 59.4%, IIIB 38.1%), which was not better than ACTS-GC. S-1 plus four cycles of Irinotecan followed by S-1 was not feasible (treatment completing rate was only 62%), and 2-year RFS was 54.7%. These results indicate that cisplatin is most promising for the partner of S-1 as adjuvant therapy that may reduce recurrence and improve survival of stage III gastric cancer. Recently, phase III study comparing eight cycles of XELOX(CLASSIC trial) to surgery alone was reported from Korea. They reported adjuvant XELOX provides superior efficacy to surgery alone. According to this result, the feasibility study of adjuvant XELOX in Japan is now planning. S-1 plus Oxaliplatin should also be verified. For HER-2-positive patients, trastuzumab is attractive for the partner of S-1 or XELOX. However, because only around 15% patients are HER-2 positive, a large-scale RCT may be difficult to conduct. In any case, it is necessary to launch the next step as soon as possible to overcome S-1 monotherapy because we are stagnant for 5 years since ACTS-GC.