To evaluate a novel anticoagulation strategy in an extracorporeal circuit, we introduce a device that induces local hypothermia as blood flows through the circuit. Using a pig model, we assessed its technical feasibility, biocompatibility, and safety. Sixteen pigs were randomly assigned to either the cooled group or the control group and underwent midline laparotomy to establish extracorporeal circulation (blood flow 500 ml/min) via the caudal vena cava for up to four hours. Blood samples were collected at baseline and at 15, 60, and 240 min during the experiment. In the cooled group, blood was cooled to 20 °C and then rewarmed to 37 °C, while in the control group, blood was maintained at 37 °C. A total of 6 cooled and 4 control pigs completed 4 h of the experiment. Our findings confirm the technical feasibility of the proposed device, which effectively maintained the required temperature differentials while keeping the pressure differentials in the circuit within 150 mmHg. No issues with circuit patency were observed. Additionally, no adverse effects were detected on erythrocyte stability. Within the limitation of the short observation period, no adverse effects were observed on renal, liver, or cardiac function. Our data suggest that local hypothermia in the extracorporeal circuit may mitigate surgery-induced inflammation.