Surface wettability trends, and blood component adhesion of some cellulose acetate phthalate/hydroxypropyl cellulose blend films are analyzed in view of adapting the system to biomedical applications. The results show that intermediate blend compositions of the corresponding films influence the surface tension parameters-controlled by the interactions occurring in the system. Increasing hydrophobicity and, implicitly, decreasing the polar surface tension components, are correlated with the adhesion/cohesion of blood components and plasma proteins. Thus, the work of spreading proteins on the hydrophobic blend surfaces indicated that albumin is not absorbed preferentially, while fibrinogen is characterized by a higher degree of adhesion on the surfaces, and also that selective adsorption of plasma proteins modifies blood compatibility. In addition, the obtained results and the ascertained antimicrobial activity of the studied blends contribute to the development of new applications in the biomedical field.