669 Background: Although adjuvant chemotherapy with S-1 has improved overall survival and progression-free survival (PFS) in patients with resected pancreatic cancer, the duration evaluation of adjuvant chemotherapy with S-1 have not established yet. Methods: We did a randomized, multicenter, phase 2 trial undertaken at 15 hospitals in Japan. Patients who were Eastern Cooperative Oncology Group performance states of 0 or 1 and aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive S-1 [40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles (6 months)] or up to eight cycles (12 months). The primary end point was overall survival rate. Secondary endpoints included PFS and safety. Results: The population consisted of 82 patients in the S-1 for 6 months group and 82 patients in the S-1 for 12 months group. The 2-year overall survival rate was 71.4% in the S-1 for 6 months group and 65.4% in the S-1 for 12 months, and the median overall survival was 31.0 months in the S-1 for 6 months group and 26.3 months in the S-1 for 12 months group [hazard ratio (HR) 1.23, 95% confidence interval (CI) 0.76-1.99, p = 0.377]. The PFS at 2 years was 56.8% in the S-1 for 6 months group, and 51.2% in the S-1 for 12 months. The HR for recurrence of S-1 for 6 months, compared with S-1 for 12 months, was 1.23 (95%CI 0.76-1.99, p = 0.392). Twenty-nine (35.3%) patients in the S-1 for 6 months group and 46 (56.0%) in the S-1 for 12 months group discontinued treatment before completion. In regard to patients completed treatment, the S-1 for 12 months group showed tendency to favorable prognosis on PFS compared with the S-1 for 6 months group (log-rank test; p = 0.175). Conclusions: In patients with resected pancreatic cancer, adjuvant chemotherapy with S-1 for 12 months is not superior to that for 6 months in terms of median overall survival and PFS. For patients who can tolerate adjuvant chemotherapy with S-1 for 6 months well, continuing treatment for up to 12 months may improve the prognosis.