AbstractHemocompatibility is a key consideration for the long‐term success of blood contacting biomaterials; hence, there is a critical need to understand the physiological response elicited from blood/nano–biomaterial interactions. In this study, we have investigated the adsorption of key blood serum proteins, in vitro adhesion and activation of platelets, and clotting kinetics of whole blood on titania nanotube arrays. Previous studies have demonstrated improved mesenchymal stem cell functionality, osteoblast phenotypic behavior, localized drug delivery, and the production of endothelial cell ECM on titania nanotube arrays. Furthermore, these titania nanotube arrays have elicited minimal levels of monocyte activation and cytokine secretion, thus exhibiting a very low degree of immunogenicity. Titania nanotube arrays were fabricated using anodization technique and the surface morphology was examined through scanning electron microscopy (SEM). The crystalline phases were identified using glancing angled X‐ray diffraction (GAXRD). Nanoindentation and scratch tests were used to characterize the mechanical properties of titania nanotube arrays. The adsorption of key blood proteins (albumin, fibrinogen, and immunoglobulin‐g) was evaluated using a micro‐BCA assay and X‐ray photoelectron spectroscopy (XPS). The adhesion and activation of platelets was investigated using live‐cell staining, MTT assay, and SEM. Whole blood clotting kinetics was evaluated by measuring the free hemoglobin concentration, and SEM was used to visualize the clot formation. Our results indicate increased blood serum protein adsorption, platelet adhesion and activation, and whole blood clotting kinetics on titania nanotube arrays. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.