Aortic cross-clamping during cardiac operations may injure the vessel wall and cause tissue lesions. This experimental study analyses the influence of the intravascular and external pressure and the duration of aortic cross-clamping on endothelial tissue damage. Fresh porcine aortas (n=20) were tested with intravascular pressures from 30 to 80 mmHg. The external clamp pressure, necessary to occlude the aorta, was applied by using the second cog of a commercial aortic clamp and cross-clamping was performed for 1 and 30 min. The observed pressure curves were compared to the histological findings. For occlusion of the aorta, an external pressure of at least 10-fold higher than the intravascular pressure (max. 812 mmHg) had to be applied. After 30 min of clamping, a complete endothelial destruction was observed, irrespective of intra-aortic pressure. The aortic media remained intact. After 1 min clamping, fractions of intact endothelial cells were left, ranging from 40 to 70% at different intra-aortic pressures. These results indicate that endothelial tissue lesions due to aortic cross-clamping are not avoidable, even in moderate clamp application. The duration of aortic cross-clamping but not intravascular pressure is the pivotal factor. The integrity of the aortic media can be preserved if low-force cross-clamping is achieved.