e15588 Background: This prospective study was performed to assess the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) with three drugs in patients with curative resection of T3 or T4 advanced gastric cancer. Methods: Patients with curative resection of clinically T3 or T4 advanced gastric cancer were required to be under 75 years of age and to have adequate organ function. After the curative resection of gastric cancer with D2 lymph node dissection and the reconstruction of the alimentary tract, HIPEC was carried out for 30 minutes with 50mg of CDDP, 10mg of MMC, and 1000mg of 5-FU in 5 L saline maintained at 42–43°C. Patients were given an adjuvant S-1 treatment after surgery. Primary endpoint of this study was overall survival. Results: A total of 29 patients were eligible. Pathologically, 8 patients had sub-serosal invasion (pT2(ss)), 18 patients had serosal invasion (pT3), and 3 patients had adjacent organ invasion (pT4). These patients included pT2(ss)pN0 (n=2), pT2(ss)pN1 (n=6), pT3pN0 (n=4), pT3pN1 (n=9), pT3pN2 (n=5), pT4pN0 (n=1), and pT4pN1 (n=2). Median follow-up period was 44 months (10–72 months). Overall 5- year survival rate in all eligible patients was 89.5%. Overall 5-year survival rate in patients with pT2(ss), pT3, or pT4 was 100%, 82.4%, or 100%, respectively. Three patients with pT3 had recurrence of pleural dissemination (n=1), lymph node metastases (n=1), or pulmonary metastases and peritoneal dissemination (n=1). A total of 7 patients had postoperative complications such as continuous pancreatic juice secretion (13.8%), abdominal abscess (10.3%), leakage of the anastomosis (3.4%), and pulmonary insufficiency (10.3%). Conclusions: The present study suggests that HIPEC with three drugs after curative resection of advanced gastric primary cancer is associated with improved overall survival with an acceptable morbidity. No significant financial relationships to disclose.