The aim of this article was to evaluate the role of hyperthermic intraperitoneal chemotherapy (HIPEC), associated or not to cytoreductive surgery (CS) in the treatment of different stages of advanced gastric cancer (AGC).Thirty seven patients with AGC who underwent 43 HIPEC from June 1992 to February 2007 were included. HIPEC used Mitomycin-C and Cisplatin for 60–90min at 41–43°C intra-abdominal temperature. The main endpoints were long-term survivals, morbidity and mortality rates.Eleven patients had no demonstrable sign of PC and constituted the Prophylactic-group, while 26 patients had macroscopic PC (PC-group). Five patients were Gilly 1 or 2 (nodules <0.5cm) and 21 Gilly 3 or 4 (nodules ≥0.5cm). In the PC-group a complete curative CS was achieved before HIPEC in 8 (PC-curative subgroup) and a palliative HIPEC in 18 patients (PC-palliative subgroup). The overall 30-days mortality was 5% (2 patients). Two patients in the Prophylactic group died within 6months after hospital discharge (overall mortality 11%). The estimated risk of death per procedure was 9%. Ten patients (27%) presented one or more complications. The median survival was 23.4months in the Prophylactic group, and 6.6months in the PC-group (p<0.05). The median survival in the PC-curative subgroup was 15 vs 3.9months in the PC-palliative subgroup (p=0.007). The median survival according to Gilly classification was significantly different (Gilly 1&2 vs Gilly 3&4, 15 vs 4months respectively, p=0.014). The global recurrence rates between the Prophylactic group and the PC-curative subgroup at 2years were 36% vs 50% respectively. The median delay to recurrence was 18.5 vs 9.7months respectively.HIPEC might be useful to improve the survival in selected patients with ACG only when a complete cytoreduction can be achieved. Despite encouraging data, prospective studies, based on larger cohorts of patients are required to assess the role of this procedure as a prophylactic treatment in patients with AGC.