Drug-eluting stents (DES) are implanted in patients to treat in-stent restenosis. Commercially available DES use polymers for coating and releasing drugs. Several studies have showed that polymer coatings cause adverse reactions. Delayed endothelialization of polymer-coated DES leads to late stent thrombosis. Recently, the potential for using self-assembled monolayers (self-assembled monolayers (SAMs)-organic constructs composed of (a) chemical groups which attach to metal surfaces, (b) long hydrocarbon chains, and (c) terminal functional groups) as an alternate drug delivery system for coronary stents has been demonstrated. In this study, the interaction of human aortic endothelial cells (HAECs) with SAMs and therapeutic SAMs (therapeutic self-assembled monolayers (TSAMs)-SAMs derivatized with the drug, flufenamic acid) was investigated. HAECs were cultured on plain glass, control, SAMs-, and TSAMs-coated titanium (Ti) and gold (Au) specimens. The viability and proliferation of HAECs were investigated using MTT colorimetric assay. The adhesion of HAECs on SAMs and TSAMs was equivalent to that of control metal surfaces and superior to that of plain glass surfaces. The cells continued to proliferate on both SAMs and TSAMs even though the rate of proliferation was slower than plain glass or control-Ti. The spreading of HAECs on TSAMs with typical polygonal shape indicated that these surfaces are conducive to endothelialization. The expression of surface adhesion protein, platelet endothelial cell adhesion molecule-1, on TSAMs indicated that the endothelial cells preserved their phenotype on these surfaces. Thus, this study demonstrated that SAMs and TSAMs do not elicit an adverse response from endothelial cells in in vitro conditions.