The basic building block of implants, including medical devices, is the biomaterial. The correlation between its structure and properties allows assessment of its potential use in medicine. The thrombogenic response of the human body, i.e., the formation of pathological clots on the implant surface, is one of the main problems encountered in biomaterial science for which thrombocytes (platelets) are responsible. It is well known that their adhesion and activation are mediated by proteins, especially human plasma fibrinogen (HPF), containing specific primary binding sites i.e., γ400-411. Therefore, strategies to control the HPF conformation upon adsorption on materials, so that specific regions of the protein remain hidden, and thus the number of active platelets is reduced to a minimum, are constantly being developed. In the present work, it has been shown that adjustment of the appropriate surface crystallographic orientation, here titanium dioxide (rutile), modulates HPF adsorption in a manner that platelets attach to a lower extent and remain non-active. Platelets are very active on the so-called titanium oxide (001) surfaces and thus promote blood clotting, whereas the opposite effect has been observed on the (110) surfaces. Fibrinogen adopts a specific conformation on the more hydrophobic (110) surface with low surface energy, which in turn limits the availability of primary amino acid sequences recognized by platelets and thus minimizes platelet adhesion. The studies presented in this work bring numerous valuable information useful for designing highly biocompatible biomaterials for implants, as it provides fundamental insights into crystallographic orientation-dependent platelet-biomaterial interactions.