Intravascular devices are widely used for vascular access but are associated with substantial risk of development of devices-related bloodstream infection (DR-BSI), which causes a considerable increase of morbidity and mortality, prolonged hospitalisation and growing medical costs. Since conventional treatment of DR-BSI fails in a significant number of cases, resulting in removal of the device, new approaches are needed to prevent bacterial colonization. In this paper, two antibiotics, rifampin and amoxicillin, have been adsorbed on polyurethanes exhibiting acidic or basic properties. The influence of the type of antibiotic-polymer interaction on the amount of adsorbed antibiotic and on the release kinetics was studied. It was seen that the antibiotic-polymer affinity increases both with the introduction in the polymer side-chain of functional groups and with the matrix hydrophilicity. The antimicrobial activity of the treated polymers, evaluated in vitro by the Kirby-Bauer test, depends on the amount of antibiotic adsorbed, on the strength of drug-matrix interaction and on the water swelling of the polymers. The inhibition zone of bacterial growth lasts only a few hours for the amoxi-coated polymers while remains at least for five months for the rifampin-coated ones. The presence of serum proteins decreases by about 30% the inhibition zone diameter of these latest matrices after two months.