e16540 Background: The aim of this study was to compare the efficacy and safety between docetaxel plus S-1 with oxaliplatin plus S-1 therapy as first-line treatment for advanced gastric adenocarcinoma. Methods: Patients, who had received docetaxel plus S-1 or oxaliplatin plus S-1 as first-line chemotherapy for advanced gastric adenocarcinoma, were retrospectively reviewed. Kaplan–Meier curve and log-rank test were used to analyze the survival. Prognostic factors were estimated by Cox regression. Adverse events (AEs) were evaluated using CTCAE 4.0. Results: One hundred and twenty-nine patients received concurrent docetaxel plus S-1, whereas 130 received oxaliplatin plus S-1. The median progression-free survival (PFS) and overall survival (OS) in docetaxel and oxaliplatin groups were 6.0 and 8.2 months ( P= 0.025), 14.7 and 15.7 months ( P= 0.697), respectively. Multivariate Cox regression suggested that chemotherapy regimen (docetaxel vs oxaliplatin; HR = 1.535, 95% CI:1.092-2.156, P = 0.014), Eastern Cooperative Oncology Group performance status (ECOG PS 3-4 vs 0-2; HR = 4.213, 95% CI: 2.246–7.903, P< 0.001), Lauren type (Intestinal vs Diffuse, HR = 0.471, 95% CI: 0.307–0.725, P= 0.001, Mixed vs Diffuse, HR = 0.649, 95% CI: 0.442–0.953, P= 0.028), and number of metastases (HR = 2.097, 95% CI: 1.421–3.095, P< 0.001) had significant effects on PFS. Multivariate Cox regression suggested that pathologic types (signet-ring cell carcinoma vs adenocarcinoma; HR = 1.688, 95% CI:1.152-2.472, P = 0.007), Lauren type (Intestinal vs Diffuse, HR = 0.637, 95% CI: 0.414–0.982, P= 0.041), number of metastases (HR = 1.7, 95% CI: 1.154–2.504, P= 0.007) had significant effects on OS.The most common grade 3-4 adverse events were leukopenia (3.1% vs 7.8%), neutropenia (7.7 vs 12.3%), anemia (13.2% vs 14.6%), thrombocytopenia (2.3% vs 10.8%), peripheral neuropathy(0.8% vs 7.8%)and Nausea/vomiting/ anorexia (1.6% vs 3.8%). Conclusions: Concurrent oxaliplatin plus S-1 therapy appears to be effective as first-line treatment in advanced gastric and has an acceptable safety profile. For patients in good physical condition, we prefer to recommend oxaliplatin combined with S-1 for treatment.