The study of protein-surface interactions is of great significance in the design of biomaterials and the evaluation of molecular processes in tissue engineering. The authors have used atomic force microscopy (AFM) to directly measure the force of attraction/adhesion of fibrinogen coated tips to mica surfaces and reveal the effect of the surrounding solution pH and ionic strength on this interaction. Silica colloid spheres were attached to the AFM cantilevers and, after plasma deposition of poly(acrylic acid), fibrinogen molecules were covalently bound on them with the help of the cross-linker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in the presence of N-hydroxysulfosuccinimide (sulfo-NHS). The measurements suggest that fibrinogen adsorption is controlled by the screening of electrostatic repulsion as the salt concentration increases from 15 to 150 mM, whereas at higher ionic strength (500 mM) the hydration forces and the compact molecular conformation become crucial, restricting adsorption. The protein attraction to the surface increases at the isoelectric point of fibrinogen (pH 5.8), compared with the physiological pH. At pH 3.5, apart from fibrinogen attraction to the surface, evidence of fibrinogen conformational changes is observed, as the pH and the ionic strength are set back and forth, and these changes may account for fibrinogen aggregation in the protein solution at this pH.