Synthetic inhibitors of trypsin-like serine proteases were covalently immobilized to polymeric materials to passivate coagulation enzymes during blood contact. The inhibitory potency of a structurally simple and larger, more complex amidine derivatives was assessed against thrombin and factor Xa. After adsorption of serum albumin, the polymer films decorated with either one of the inhibitors were found to scavenge thrombin-with a higher affinity in the case of the larger inhibitor-but not factor Xa. Both inhibitor-containing coatings showed a significantly reduced thrombogenicity, coagulation activation, as well as complement activation when incubated with freshly drawn human whole blood in vitro. The authors conclude that the introduced principle offers a promising approach for hemocompatible materials for short term applications. Even rather simple inhibitors can be successfully employed for that purpose.