Background: Nivolumab plus chemotherapy (N+C) in the first-line treatment and nivolumab monotherapy in the third- or later-line have shown survival benefit in patients with unresectable advanced or recurrent G/GEJ cancer. Adjuvant chemotherapy after D2 or more extended gastrectomy is a widely used standard of care for pStage III G/GEJ cancer in Asia. However, standard adjuvant chemotherapy has shown limited efficacy for pStage III G/GEJ cancer. ATTRACTION-5 is the first phase 3 study to evaluate an immune checkpoint inhibitor in combination with adjuvant chemotherapy for pStage III G/GEJ cancer. Here, we report the first confirmatory results of N+C as postoperative adjuvant treatment. Methods: The ATTRACTION-5 study is a multicenter, double-blind, randomized study conducted in Japan, Korea, Taiwan, and China. We enrolled patients with pStage III G/GEJ cancer who had undergone D2 or more extended gastrectomy. Investigators selected an appropriate adjuvant chemotherapy (tegafur/gimeracil/oteracil [S-1] therapy or capecitabine plus oxaliplatin [CapeOX] therapy) for each patient, and thereafter patients were randomly assigned (1:1) to the N+C or placebo plus chemotherapy (P+C) arm, using the allocation factors of country and disease stage. The primary endpoint was centrally-assessed relapse-free survival (RFS). The sample size was calculated, based on the results of the ACTS-GC study and the CLASSIC study (The assumed hazard ratio [HR], 0.67; the assumed 3-year RFS, 71% vs 60%). Secondary endpoints were investigator-assessed RFS, overall survival (OS), and 3-year RFS and OS rates. Results: A total of 755 patients underwent randomization from February 2017 to August 2019: 377 were assigned to the N+C arm and 378 to the P+C arm. The final analysis of RFS was performed based on the clinical data cutoff of August 2022, with the minimum follow-up of 36 months after the last patient was randomized. The primary efficacy endpoint of centrally-assessed RFS was not met (HR, 0.90; 95.72% CI, 0.69–1.18; P=0.4363), with the 3-year RFS rates of 68.4% (95% CI, 63.0–73.2) in the N+C arm and 65.3% (95% CI, 59.9–70.2) in the P+C arm. The completion rate of the planned postoperative adjuvant treatment was 61.5% in the N+C arm and 71.4% in the P+C arm. Incidences of grade≥3 TRAEs, serious TRAEs, and TRAEs leading to discontinuation were 54.4%, 25.3%, and 9.2%, respectively, in the N+C arm and 46.8%, 10.7%, and 3.5% in the P+C arm. Conclusions: The ATTRACTION-5 study of N+C vs P+C in patients with pStage III G/GEJ cancer after D2 or more extended gastrectomy did not meet the primary endpoint of RFS. The safety profile in the ATTRACTION-5 study was consistent with its known safety profile. Clinical trial information: NCT03006705.