Purpose <p>Postoperative chemoradiotherapy (POCRT) and perioperative chemotherapy (PECT) have been established as the preferred treatment modalities according to the INT0116 and MAGIC studies, respectively. There is limited evidence about the superiority of one over the other. Therefore, we conducted this retrospective study to compare efficacy and toxicity between PECT and POCRT in localized gastric cancer.</p> Methods <p>A&#xa0;total of 200 patients with localized gastric cancer (134 patients in the POCRT group and 66&#xa0;patients in the PECT group) were retrospectively recruited from the medical oncology and radiotherapy departments of the South Egypt Cancer Institute during the period from January 2010 to January 2020.</p> Results <p>The median disease-free survival (DFS) of patients receiving POCRT was significantly longer than for those in the PECT arm (<i>p</i> &lt; 0.001), with no statistically significant difference in median overall survival (OS) between the groups (<i>p</i> = 0.402) during a&#xa0;median follow-up of 40&#xa0;months. Patients with clinically negative lymph nodes (<i>p</i> &lt; 0.001) and signet ring carcinoma (<i>p</i> &lt; 0.001) treated with POCRT had significantly lower recurrence rates than those treated with PECT, while no statistically significant difference was shown between the two groups in patients with clinically positive lymph nodes (<i>p</i> = 0.331). Patients treated with PECT had a&#xa0;higher incidence of thrombocytopenia (<i>p</i> = 0.007), neutropenia (<i>p</i> &lt; 0.001), and neuropathy (<i>p</i> = 0.033) compared to POCRT-treated patients. Multivariate analysis showed that PECT was independently associated with lower DFS (hazard ratio 1.956, 95% confidence interval 1.352–2.830; <i>p</i> &lt; 0.001).</p> Conclusion <p>In patients with resectable gastric cancer, POCRT improved DFS compared to PECT.</p>