Adjuvant chemotherapy and/or chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive gastric cancer.The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4-weeks-on/2-weeks-off) for one year, S-1 (2-weeks-on/1-week-off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for six months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3-years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared to S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146).A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 vs. SOX, 0.692 (P=0.042) and S-1 vs. SOXRT, 0.724 (P=0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971, P=0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable.In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX, or SOX/RT was effective in prolonging DFS, when compared to S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2-gastrectomy.