BackgroundTo determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status.MethodsIn this retrospective analysis, the National Cancer Database was used to identify resected non‐metastatic GC (2006−2016). Patients were stratified by clinical nodal status—negative (cLN−) and positive (cLN+). In patients with cLN− disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN− and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan−Meier survival estimate, log‐rank test, and multivariable Cox proportional hazards analysis were performed.ResultsWe identified 7827 patients (cLN− 4828; cLN+ 2999). On multivariable analysis in patients with cLN− disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70−0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88−1.40, p = 0.39) and POC (n = 341) in patients with pLN− disease. On multivariable analysis in all patients with cLN− disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75−0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70−1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677).ConclusionPostoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node‐negative disease to pathologically node‐positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.