Background: Gastrectomy with D2 dissection and adjuvant chemotherapy is currently the standard treatment for locally advanced gastric cancer (LAGC) in Asian countries. However, administering chemotherapy with sufficient intensity after gastrectomy is often challenging. Thus, several trials have been undertaken to demonstrate the efficacy of neoadjuvant chemotherapy (NAC). NAC-SOX regimen for LAGC has been already shown to reduce distant micro-metastasis and to improve the R0 resection rate by tumor shrinkage in Asian trials. However, there have been few studies of the feasibility of NAC-SOX for elderly patients with LAGC. KSCC1801 is a phase II study to evaluate the safety and efficacy of NAC-SOX in elderly patients aged 70 years or over with LAGC. Methods: Patients received three cycles of SOX as neoadjuvant chemotherapy followed by gastrectomy with D2 dissection. Oxaliplatin was administered intravenously (130 mg/m²) on day 1, and S-1 was administered orally (80- 120 mg/day) for 14 days followed by 7-day rest period. The primary endpoint was the dose intensity (DI). A sample size of 25 was set according to a one-sided significance level of 0.025 and a power of 80% on the basis of a one-sample t-test and assuming a null hypothesis of a 75% DI and an alternative hypothesis of an 85% DI with an estimated standard deviation of 14%. The secondary endpoints were safety, R0 resection rate, response rate, overall survival, and relapse-free survival. Results: Twenty-six patients were enrolled in this study. The median age was 74.5 years. The median DI in NAC-SOX was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC could be performed in 25 patients (96.2%), of whom 23 (88.5%) underwent gastrectomy with D2 dissection. The R0 resection rate was 92.3% and the pathological response rate (≥grade 1b) was 62.5% [95% confidence interval: 40.6 - 81.2]. The major adverse events (≥grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%) and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. One treatment-related death occurred, probably due to severe diarrhea and dehydration. Conclusions: NAC-SOX was feasible and promising even in elderly patients. Systemic management and more careful monitoring of adverse events are necessary for elderly patients. Clinical trial information: jRCTs071180001.