Background: Despite advances in surgery and adjuvant chemotherapy, intraperitoneal recurrence is highly frequent in gastric cancer (GC) with a dismal prognosis. In this retrospective study, we aimed to evaluate the effectiveness of adding simplified prophylactic heated intraperitoneal chemotherapy (sp-HIPEC) between surgery and systemic chemotherapy. Methods: Clinical data of 170 patients diagnosed as having locally advanced GC and receiving D2 surgery were retrospectively reviewed. Of the patients, 99 received sp-HIPEC, followed by systemic postoperative chemotherapy, and 71 received only systemic postoperative chemotherapy. Overall survival and recurrence rates between the groups were compared. Results: The median survival was 30.3 and 17.2 months for the sp-HIPEC and systemic groups, respectively (hazard ratio, 0.56; 95% CI, 0.10-0.97). The 3- and 5-year survival rates were 48.2% vs 41.4% and 22.9% vs 14.4%, respectively. Moreover, adding sp-HIPEC significantly reduced peritoneal relapse rate.Both regimens were well tolerated. Conclusions: Adding sp-HIPEC between surgery and systemic chemotherapy may benefit the overall survival without causing additional treatment toxicity.