Meng-Long Zhou,1,2,* Wang Yang,1,2,* Ya-Qi Wang,1,2,* Miao Mo,2,3 Ran Hu,1,2 Yan Wang,1,2 Jia-Ning Yang,1,2 Gui-Chao Li,1,2 Ya-Nong Wang,2,4 Zhen Zhang1,21Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 4Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workPurpose: N3 gastric cancer (GC) is characterized by a heavy burden of lymph node metastasis and a high postoperative recurrence rate. The role of radiotherapy in this group of patients remains undetermined. The purpose of this study was to compare the effectiveness of adjuvant chemoradiotherapy (CRT) and adjuvant chemotherapy (ChT) for N3 GC after D2/R0 resection.Patients and methods: From January 2004 to December 2015, patients with N3 GC in the database of Fudan University Shanghai Cancer Center were retrospectively reviewed. The eligible patients were enrolled in an adjuvant CRT group and an adjuvant ChT group. Four different methods based on a propensity score model were used to balance the baseline characteristics. Then, survival analyses between the two groups were performed in addition to patterns of recurrence and subgroup analyses.Results: In total, 175 and 365 eligible patients were enrolled into the CRT and ChT groups, respectively. After balancing, the disease-free survival (DFS) of patients in the CRT group was significantly better than that of patients in the ChT group (p=0.021). Subgroup analyses showed that patients with N3a GC benefitted from adjuvant CRT.Conclusion: Compared with adjuvant ChT, adjuvant CRT can further improve the DFS of patients with N3 GC after D2/R0 resection. Patients with lymph node metastases should be further stratified when selecting patients for adjuvant CRT.Keywords: stomach neoplasms, gastrectomy, chemoradiation, propensity score, survival analysis