Background: S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in Japan. In patients with HER-2 positive AGC, combined administration of fluoropyrimidine plus cisplatin and trastuzumab is the standard treatment. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. Especially, these disadvantages of cisplatin are noticeable in elderly patients. We have already reported the results of the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC. In this time, we report the survival results of this study. Methods: Patients, 65 years or older, with HER-2 positive AGC received S-1 (80-120mg per day) orally on days 1-28 of a 42-day cycle and trastuzumab (first time: 8 mg/kg, from 2nd onward: 6 mg /kg) intravenously on day 1 of a 21-day cycle. Results: A total of 51 patients were enrolled. One patient was ineligible, one patient did not receive study treatment, therefore in the full analysis set of 49 patients, the median age was 71 years (range: 65-85) and ECOG PS was 0/1/2: 32/14/3. The confirmed RR (CR/PR/SD/PD: 2/18/21/8) was 40.8% (80% confidence interval (CI): 31.8-49.8%, 95% CI: 27.1-54.6%), and the null hypothesis was rejected. Median follow up period was 10.6 months. Median OS was 15.8 months (95%CI: 9.13-20.37). Median PFS was 5.1 months (95%CI: 3.78-5.55), and TTF was 4.0 months (95%CI: 3.09-5.39). Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death. Conclusions: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects, as well as promising survival results in elderly patients with HER-2 positive AGC. Clinical trial information: 000007368.