Background/Aims Adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin (CAPOX) is considered standard treatment for patients with stage II or III gastric cancer after D2 lymph node dissection in East Asian countries. However, the efficacy of adjuvant chemotherapy in elderly patients with gastric cancer remain unclear. This study aimed to compare the efficacies of adjuvant chemotherapy S-1 versus capecitabine plus oxaliplatin (CAPOX) for elderly patients with gastric cancer after D2 lymph node dissection. Methods This retrospective multicenter cohort study enrolled 983 patients who underwent curative gastrectomy and consecutively received adjuvant chemotherapy with S-1 or CAPOX for stage II or III gastric cancer at 27 hospitals in Korea between February 2012 and December 2013. Long-term oncologic outcomes, including overall survival and disease-free survival rate, were analyzed. Results Of the 983 patients, 254 (25.8%) patients were elderly (aged 70 or older). There was no significant difference in the survival rate between the S-1 and the CAPOX group in non-elderly patients (OS [overall survival]; p=0.570, DFS [disease-free survival; P=0.281). However, the survival rates for the CAPOX group were significantly lower than for the S-1 group in elderly patients (OS; p<0.001, DFS; P<0.001). The CAPOX group (Hazard ratio; 1.891, 95% Confidence interval; 1.072-3.333, p=0.028) was determined as independent prognostic factor for OS and DFS in elderly patients. Conclusions Adjuvant chemotherapy with S-1 showed better survival outcomes compared with CAPOX for elderly pa-tients with stage II or III gastric cancer.