Experimental studies and clinical experience suggest that the combination of positive end-expiratory pressure (PEEP) ventilation and intra-abdominal hypertension might alter splanchnic hemodynamics to a significantly greater degree than the effect of either of them alone. Therefore, we assessed the intestinal and hepatic hemodynamics in two steps of PEEP ventilation, adding tense pneumoperitoneum in a pig model. The hepatic artery, portal vein, and superior mesenteric artery blood flow, as well as the hepatic and intestinal mucosal microcirculation, and the hepatic pO2 and intestinal mucosal pH, were assessed before, then with 5 cmH2O and 10 cmH2O PEEP alone, and in combination with a 12-mmHg pneumoperitoneum, in ten domestic pigs. Statistical analysis of the hepatic and intestinal measurements revealed a significant decrease (P = 0.001) in all parameters in relation to the baseline, during the 5-cmH2O and 10-mmH2O PEEP ventilation period. The addition of 12 mmHg intra-abdominal pressure led to an extreme deterioration in all parameters (P = 0.001), in relation to both the baseline and the 10-cmH2O PEEP measurement. These findings demonstrate that PEEP and intra-abdominal hypertension act cumulatively on the abdominal viscera, producing conditions of extremely low hypoperfusion and ischemia.