The aim of this study was to investigate the efficacy and safety of an alternating regimen of S-1 plus low-dose cisplatin and S-1 alone as adjuvant therapy in patients with advanced gastric cancer. The study group comprised 100 patients with stage IIIA, stage IIIB, or stage IV. Patients postoperatively received three 5-week cycles of chemotherapy. In the first cycle, S-1 (80 mg/m(2)) was given daily for 3 weeks, followed by 2 weeks of rest, and low-dose cisplatin (10 mg) was given on days 1 to 5 and 8 to 12. In the second and third 5-week cycles, S-1 alone was given. The primary endpoints were median survival time, and survival at 1 and 3 years. Secondary endpoints were safety and overall response rates. Median survival time was 18 months in stage IV and 32 months in stage IIIB. The rates of survival at 1 and 3 years were 68.7% and 30.6% in stage IV, 100% and 68.4% in stage IIIA, and 100% and 46.6% in stage IIIB, respectively. Adverse events of grade 3 or 4 occurred in 14% of the patients. The overall response rate of target lesions was 54%. Our regimen is effective and safe for adjuvant therapy in patients with curatively resected stage III gastric cancer.