Background: Adjuvant chemotherapy following curative gastrectomy is recommended for patients with pStage II or III, except pT3 (ss), N0 gastric cancer in Japan. This study aimed to compare the efficacy of postoperative adjuvant chemotherapy with S-1 versus SOX/XELOX for pStageIII gastric cancer. Methods: Between January 2015 and December 2018, 51 patients with pStage III gastric cancer underwent curative gastrectomy. The combination therapy group received a combined SOX and XELOX regimen as follows: (1) SOX regimen: 130 mg/m² of oxaliplatin on day 1 every 3 weeks combined with 40 mg/m² of S-1 twice daily on days 1–14 every 3 weeks; (2) XELOX regimen: 130 mg/m² of oxaliplatin on day 1 every 3 weeks combined with 1000 mg/m² of capecitabine twice daily on days 1–14 every 3 weeks. We evaluated their hospital records retrospectively. The indication of SOX/XELOX regimens was based on PS and intent of patients. Results: The S-1 group comprised 28 cases (pStage III A/B/C: 12/8/8), while the SOX/XELOX group comprised 23 cases (pStage III A/B/C: 4/10/9). There was no difference in age, sex, comorbidity, prognostic nutritional index and stage between two groups. The 2-year DFS of the S-1 group and the SOX/XELOX group were 58.6% and 71.7%, respectively (p = 0.367). Subgroup analysis showed that the 2-year DFS of patients with pStage IIIC gastric cancer in the S-1 group was significantly lower than the SOX/XELOX group (S-1 vs. SOX/XELOX: 25.9% vs. 78.7%, p = 0.041). As concerns adverse effects (CTCAE ver 4.0), peripheral sensory neuropathy was significantly higher in the SOX/XELOX group than in the S-1 group (S-1: grade I/II 3.6%/0% vs. SOX/XELOX: grade I/II 21.7%/34.8%, p < 0.001), although the other adverse effects did not differ between the two groups. Conclusions: SOX/XELOX therapy may be more useful than S-1 therapy for more advanced tumors among pStage III gastric cancers.