Abstract Purpose The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery. Method Data were retrospectively collected from consecutive patients who underwent S-1 adjuvant chemotherapy following curative pancreatectomy between January 2016 and December 2018. Four-courses and > 4 courses cohorts were compared for overall survival (OS) as a primary outcome, and relapse-free survival (RFS) and adverse event incidence as secondary outcomes. Results Four-courses and > 4 courses cohorts comprised 99 patients and 64 ones, respectively. TNM stage (stage II vs. I: HR, 2.125; 95% CI, 1.164–4.213; P = 0.015), duration of S-1 administration (4 vs. > 4 courses: HR, 3.113; 95% CI, 1.531–6.327; P = 0.002) and tumor grade (G3 vs. G1/2: HR, 3.887; 95% CI, 1.922–7.861; P 4 courses cohort was significantly prolonged compared with that of 4 courses cohort (4 vs. > 4 courses: HR, 2.284; 95% CI, 1.197–4.358; P = 0.012), especially for patients in TNM stageII (4 vs. > 4 courses: HR, 2.906; 95% CI, 1.275–6.623; P = 0.011).RFS and adverse events incidence did not signifcantly difer between both cohorts. Conclusion Prolonged duration of S-1 intake is beneficial to prognosis of patients with PDAC resection.