Background: Prevention of recurrence after curative (R0) surgery is one of the most important subjects to be resolved for gastrointestinal (GI) cancers. We have previously shown that hyperthermic intraperitoneal chemotherapy (HIPEC) following R0 gastrectomy is effective for preventing peritoneal recurrence. However, little is known about the preventive effect of HIPEC for GI cancers on hepatic recurrence. The aim of this study was to compare hepatic or peritoneal recurrence-free survival between patients with or without adjuvant HIPEC after R0 gastrectomy for an advanced gastric cancer (GC). Methods: Patients with advanced GC who underwent gastrectomy with a curative intent in the Shiga University of Medical Science hospital between 1998 and 2012 were included in this single center, retrospective, propensity score-matched cohort study. Cox proportional hazards regression models were used to evaluate the association between adjuvant HIPEC and hepatic or peritoneal recurrence-free survival. The Kaplan-Meier method was used to calculate the survival rate. P values < 0.05 were considered statistically significant. HIPEC was performed using CDDP and MMC, or combined with 5-FU in 5 L of perfusate of saline maintained at 42–43°C for 30 min. Results: A total of 186 patients with an advanced GC, in which the pathological depth of invasion was beyond the muscularis propria, were included in the study. There was no significant difference in clinicopathological factors between the matched cohorts (with or without HIPEC). There were significant differences in the hepatic recurrence-free survival (hazard ratio [HR] for with HIPEC versus without HIPEC: 0.10, 95%CI: 0.012 to 0.83, P: 0.033) and peritoneal recurrence-free survival (HR: 0.20, 95%CI: 0.068 to 0.61, P: 0.005). The 3- and 5-year overall survival rate was 94.0% and 86.8% in patients with HIPEC and 59.1% and 53.4% in patients without HIPEC (log-rank: P< 0.0001). Conclusions: Adjuvant HIPEC performed with R0 gastric surgery showed a preventive effect on hepatic recurrence, as well as peritoneal recurrence and survival benefits for patients with advanced GC compared with R0 surgery alone.