Background: Elderly patients are often intolerable in the combination with cytotoxic agents. Therapy with S-1 alone is a key option for initial chemotherapy for Japanese elderly patients with unresectable gastric cancer in clinical practice. However, there are some cases in which the antitumor effects with S-1 alone are insufficient. We aimed to investigate the efficacy and safety of S-1 plus ramucirumab therapy to elderly patients with advanced/recurrent gastric cancer. Methods: Patients aged 70 years and older with previously untreated unresectable or recurrent gastric cancer patients were included in Japan. They received S-1 therapy (40-60 mg twice daily for 28 days, every 6 weeks) plus ramucirumab therapy (8 mg/kg, every 2 weeks) until disease progression. The primary endpoint was the one-year survival rate and null hypothesis of one-year survival was set as 40%, which is the lower bound of the 95% confidence interval in previously reported studies on S-1 therapy. The secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), and safety. Results: Between September 2017 and November 2019, 48 patients were enrolled in this study. The characteristics of patients were male/female: 34/14, median age: 77.5 years (range: 71-87), and PS (0/1): 20/28. The one-year survival rate was 65.2% (95% confidence interval 49.8-78.6%), which means this trial met the primary endpoint. The median OS and PFS were 16.4 months (95%CI:12.0–20.7) and 5.8 months (95%CI:4.0–7.2), respectively. The best RR (CR+PR) was 60.9%. The frequent grade 3 or grade 4 adverse events were neutropenia (27.7%), anorexia (23.4%), anemia (19.1%), hypertension (14.9%), leucopenia (12.8%) and hypoalbuminemia (12.8%). Conclusions: Based on the observed efficacy and safety, S-1 plus ramucirumab is an appropriate first-line treatment for elderly patients with advanced/recurrent gastric cancer. Clinical trial information: UMIN000028309.