The intra-arterial application of radiographic contrast media (RCM) can induce decreases of blood flow velocity in downstream capillaries as well as a decrease in the tissue oxygen tension. It is unclear whether changes in endothelial cell morphology contribute to the observed microcirculatory disorders. Four RCMs (Iodixanol320, Iohexol350, Iopromide370, and Imeron350) were added to the culture medium of human umbilical venous endothelial cells (HUVEC) and used for short-term incubation studies of these cells. Addition of Iohexol (p=0.6377) and Iodixanol (p=0.6309) did not affect the HUVEC height 1.5 min after incubation in the modified cell culture media supplemented with 30% v/v of the respective RCM. Strong buckling and increased endothelial height appeared after incubation in Iopromide-supplemented medium (the cell height increased by 95% compared to cells incubated under control conditions; p=0.0065). Addition of Iomeprol-supplemented medium caused an increase by 61.6% compared to cells incubated under control conditions; p=0.0051. After 5 min of incubation in any of the RCM-supplemented media, there was no difference in HUVEC height in comparison to incubation in control standard culture media (each p value>0.05). The tremendous buckling caused by Iopromide and Iomeprol, coinciding with an echinocyte formation of erythrocytes might be the reason why a bolus injection of Iopromide in vivo into the left coronary artery was followed by a 50% decrease of oxygen partial pressure in the supplied tissue.