OBJECTIVES: This study aims to assess the association between adjuvant radiotherapy and the development of second primary malignancies (SPMs) and identify its determinants in patients who have undergone surgical treatment for gastric cancer. DESIGN: Retrospective cohort study using the Surveillance, Epidemiology and End Results (SEER) database. SETTING: Cohorts (18 registries, 2000-2018, from SEER) were screened for any malignancy that developed after sufficient latency from diagnosis of surgically treated non-metastatic gastric cancer. PARTICIPANTS: 24 777 surgically treated gastric cancer cases were included in the cohort. Among them, 6128 patients underwent adjuvant radiotherapy. OUTCOME MEASURES: The cumulative incidence of SPMs was estimated using Fine and Gray's competing risk model and the radiotherapy-correlated risks were calculated using Poisson regression analysis. RESULTS: Among patients with sufficient latency, there was no significant association between radiotherapy and the risk of developing second primary solid malignancies (relative risk=1.05, 95% CI 0.83 to 1.33) or haematological malignancies (relative risk=1.17, 95% CI 0.62 to 2.11). Interestingly, radiotherapy was associated with a reduced cumulative incidence of second lung and bronchus cancer compared with no radiotherapy, with a 15-year incidence of 1.4%-3.17% (p<
0.05). Radiotherapy was not associated with a significant increase in standardised incidence ratios of SPMs. CONCLUSIONS: Adjuvant radiotherapy was not associated with an increased risk of developing SPMs in surgically treated patients with gastric cancer. Clinical trials are warranted to further verify the findings.