Background: Base on the ACTS-GC trial, adjuvant chemotherapy with S-1 at a dose of 80 mg/m²/day (4 weeks on and 2 weeks off, repeated for one year) is the standard care for stage II/III gastric cancer (GC) patients (pts) after D2 gastrectomy. As Japan has the most aged population in the world, the actual number of elderly GC pts is still increasing. While elderly pts population is heterogeneous and is conceptually composed of “fit”, “vulnerable” and “frail” pts, full-dose adjuvant chemotherapy tends to be given to fit elderly pts in clinical practice. However, it has not been determined yet whether S-1 should be administered to vulnerable pts over 80. Actually, according to the questionnaire survey conducted on 58 institutions of Stomach Cancer Study Group of Japan Clinical Oncology Group, S-1 was administered on only 15% to stage II/III pts > = 80 years old suggesting that surgery alone is generally considered as community standard for vulnerable pts. It is an urgent need to establish the standard adjuvant treatment of the vulnerable elderly GC pts. Methods: The study is designed to confirm the superiority of S-1 treatment group over surgery alone group focusing on vulnerable > = 80 years old pts in stage II / III GC after curative resection. The “vulnerable” is defined in this study based on the three factors [creatinine clearance (Ccr), weight loss, type of surgery] considered to have the most influence on compliance of S-1, that is Ccr > = 30ml/min, weight loss < 15% and total gastrectomy, or 80 > Ccr > = 30ml/min, weight loss < 15% and other than total gastrectomy. Initial dose was reduced by 1 rank from the standard dose. The primary endpoint is overall survival (OS) and the secondary endpoints are relapse free survival, time to treatment failure, treatment continuity, relative dose intensity and adverse events. We assume expected 3-year OS in surgery alone arm will be 55% and S-1 treatment will improve the survival by more than 10%. 370 pts are required to provide 75% of power and 5% one-sided alpha error, with 4 years accrual and 3 years of follow up period. The trial has started from January 2017. Clinical trial information: UMIN000025742. Clinical trial information: 000025742.