The thrombogenicity of membrane oxygenators as well as clotting parameters profiles, using standard human clotting tests, was analyzed in calves and pigs during 6 h perfusion. Three calves and 3 pigs were connected to extracorporeal circulation with standard heparinization. Blood samples were taken for coagulation variables throughout perfusion, and oxygenators were examined for clot deposits at the end of the experiment. Two out of 3 oxygenators of the calf group presented clot deposits while none in the pig group did. Baseline coagulation variables of pigs showed values similar to those of humans while neither extrinsic nor intrinsic pathways could be activated in calves with standard human coagulation tests. The calf model, in conclusion, was confirmed to be a difficult model for the testing of extracorporeal circulation device resistance to thrombus formation, which is, however, not reflected by standard human coagulation tests. The pig model is a better model in which both coagulation pathways could be activated with standard human coagulation tests.