Background: Postoperative S-1 (80 mg/m²/day for 4 weeks and 2 weeks rest in one course) for 1 year corresponding to 8 courses is a standard adjuvant chemotherapy for pathological stage (pStage) II gastric cancer. To shorten the duration of S-1 chemotherapy, we conducted a phase III trial to confirm non-inferiority in relapse-free survival (RFS) of 4 courses of S-1 to 8 courses of S-1 for pStage II gastric cancer. When 590 patients were enrolled, the study was closed at the first interim analysis because of futility. The RFS at 3 years was 89.8% for 4-courses and 93.1% for 8-courses (HR 1.84, 95% confidence interval (CI) 0.93-3.63). This is a final 5-year follow-up results of this study. Methods: Key eligibility criteria were pStage II except for T1 and T3N0 (7^th edition of TNM), ECOG performance status 0-1, R0 resection with D2 lymph node dissection for >clinical stage (cStage) II or D1+ lymph node dissection for cStage I, within 7 weeks after surgery, and age between 20 and 80 years. The total sample size was determined to be 1,000 with a 3-year RFS of 85% in both arms and non-inferiority margin of hazard ratio (HR) of 1.37, with one-sided alpha of 5% and 80% power. Results: Between Feb 2012 and Mar 2017, 590 patients, 295 for each arm, were enrolled. When closing the study, the patients who were allocated to the 4-courses arm were informed of the primary results and the recommendation to continue S-1 until 8 courses as an off-protocol when they were receiving S-1. The cut-off date for the final follow-up data was March 22, 2022 with a median follow-up period for surviving patients of 6.0 years (IQR; 5.0-7.2). In 4-courses arm, 27 patients were receiving S-1 when the study was closed at the interim analysis. Among them, 22 patients expressed their will to continue until 8 courses. The RFS at 3/5 years was 90.1%/85.6% for 4-courses and 92.2%/87.7% for 8-courses (HR 1.27, 95% CI 0.85-1.89). The overall survival at 3/5 years was 93.2%/88.6 for 4-courses and 94.9%/89.7 for the 8-courses (HR 1.12, 95% CI 0.72-1.75). The HR of the cumulative incidence of the recurrence was 1.38 (95% CI 0.85-2.24) for the 4-courses against 8-courses. Recurrence was frequently observed in patients who received up to 4 courses of S-1 (38 for 4-courses vs. 28 for 8 courses). The HR of the cumulative incidence of the peritoneal recurrence was 1.54 (95% CI 0.82-2.89) for the 4-courses against 8-courses. Conclusions: This final follow-up data confirmed the primary results presented at the interim analysis. S-1 adjuvant chemotherapy for 1 year for pStage II gastric cancer is highly recommended. Clinical trial information: 000007306.