In patients with stage II/III gastric cancer, tumors often recur even after curative D2 gastrectomy followed by adjuvant S-1 chemotherapy. The objective of this retrospective study was to clarify the prognostic factors in these patients that might be useful for future patients. Overall survival (OS) was examined in 82 gastric cancer patients who underwent curative D2 surgery; were diagnosed with stage IIA, IIB, IIIA, IIIB, or IIIC pathologically; and received adjuvant S-1 after surgery between June 2002 and March 2010. When length of OS was evaluated by the log-rank test, significant differences were observed with regard to macroscopic tumor diameter and the depth of tumor invasion. A macroscopic tumor diameter >70 mm was regarded as a critical point of classification considering survival. Univariate and multivariate Cox's proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The 5-year survival was 64.9% in patients with a macroscopic tumor diameter <70 mm, and 33.1% in patients with a macroscopic tumor diameter ≥70 mm (P = 0.022). The macroscopic tumor diameter was the most important prognostic factor for survival in patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant S-1 chemotherapy. Prognostic factors can be affected by adjuvant chemotherapy.