Objective. Fluid shear stress (FSS) is crucial for maintaining endothelial cell expression of nitric oxide (NO) synthase (NOS-3) and, consequently, NO production in vivo. The defective -786C variant of the nos-3 gene promoter is insensitive to FSS resulting in reduced NO formation and, in the long run, endothelial dysfunction. The aim of this study was to investigate whether this genetically determined endothelial dysfunction leads to impaired leukocyte–endothelial cell interactions. Methods. Primary human umbilical cord vein endothelial cells (EC) were isolated and genotyped for the nos-3 gene T-786C single nucleotide polymorphism. For transmigration studies, genotyped ECs were exposed to FSS and subsequently seeded on filter inserts (pore size 8mm) to re-establish a tight monolayer. The human monocytic cell line THP1 was used to analyse MCP-1-stimulated (30ng/mL) transmigration. As readouts (i) the number of transmigrated cells and (ii) pro-inflammatory gene expression according to real-time PCR was analysed in monocytes. Results. As expected, CC genotype ECs revealed a reduced basal and FSS-stimulated capacity to synthesise NO. However, exposure to FSS effectively suppressed THP-1 cell transmigration through all EC monolayers, regardless of their genotype. Moreover, pro-inflammatory gene expression in the transmigrated monocytes was lowest after transmigration through a CC genotype EC monolayer. Therefore, we hypothesised that CC genotype EC develop compensatory mechanisms to offset their insufficient NO supply. In fact, only CC genotype ECs revealed an increase in superoxide dismutase-2 expression and a greater sensitivity to cyclooxygenase-1 blockade in response to FSS as their TT genotype counterparts. Conclusion. Despite an impaired NO synthesis capacity, CC genotype ECs reveal a robust anti-inflammatory phenotype pointing towards compensatory mechanisms that include an increased scavenging of superoxide anions and an enhanced release of prostacyclin.