During catheter ablation of cardiac tissue, the insulting stimulus may damage and activate the blood. Specifically activation of platelets and the clotting system is a potential risk by their formation of thrombi. In this study the effect of two different techniques, a radiofrequency and a cryo-application procedure, on the activation of platelets and clotting in an in vitro blood circulation model was investigated. The radio-frequency procedure induced significantly more blood cell damage, platelet activation and clotting than did the cryo-application procedure. Macroparticles were circulating in blood after the radiofrequency procedure. In the cryo procedure, blood damage was limited to the frozen blood spherule around the tip of the catheter. It is concluded that at least in those circumstances where blood is directly contacting the tip of the radiofrequency or cryo-application catheter, the latter is more safe with regard to thrombus formation.