BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) achieve good results in selected patients with peritoneal carcinomatosis. High intra-abdominal pressure could enhance the penetration of chemotherapy drugs. The aim of this study was to compare the effects of high pressure and hyperthermia when used separately and when combined in terms of blood and tissue absorption of oxaliplatin in a swine model of intraperitoneal chemotherapy. METHODS: Four groups of 5 pigs each underwent laparotomy and open intraperitoneal chemotherapy with oxaliplatin at a constant concentration (150 mg/L) for 30 minutes in normothermia and atmospheric pressure (group 1), or hyperthermia (42°C) and atmospheric pressure (group 2), or normothermia and high pressure (25 cm H2O) (group 3), or hyperthermia and high pressure (group 4). High pressure was achieved thorough a water column over the abdomen. Systemic absorption and abdominal tissue mapping of the penetration of oxaliplatin in each group were studied. RESULTS: Blood concentrations of oxaliplatin were similar in the different groups. Hyperthermia achieved higher concentrations in visceral surfaces (P = 0.0014), but not in parietal surfaces. High pressure enhanced diffusion of the drug in both the visceral and parietal peritoneum (P = 0.0058 and P = 0.0044, respectively). The combination of hyperthermia and high pressure significantly increased the penetration of oxaliplatin and achieved the highest tissue concentrations (10.39 mg/kg vs 5.48 mg/kg; P = 0.00001 in the visceral peritoneum, and 66.16 mg/kg vs 35.62 mg/kg; P = 0.0003 in the parietal peritoneum). CONCLUSIONS: Open high-pressure HIPEC with oxaliplatin is feasible in the pig. Hyperthermia enhances diffusion in the visceral peritoneum, whereas high pressure is effective in the visceral and parietal peritoneum. The combination of the two achieves the highest tissue concentrations of oxaliplatin.