AbstractThe formation of a calcium phosphate layer on the surface of the SiO2–CaO–P2O5 glasses after immersion in simulated body fluid (SBF) generally demonstrates the bioactivity of these materials. Grafting of the surface by chemical bonding can minimize the structural changes in protein adsorbed on the surface. Therefore, in this study our interest was to evaluate the bioactivity and blood biocompatibility of the SiO2–CaO–P2O5 glasses after their surface modification by functionalization with aminopropyl‐triethoxysilane and/or by fibrinogen. It is shown that the fibrinogen adsorbed on the glass surfaces induces a growing of the apatite‐like layer. It is also evidenced that the protein content from SBF influences the growth of the apatite‐like layer. Furthermore, the good blood compatibility of the materials after fibrinogen and bovine serum albumin adsorption is proved from the assessment of the β‐sheet–β‐turn ratio. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 261–272, 2015.