The emergence and spread of antibiotic resistance across microbial species necessitates the need for alternative approaches to mitigate the risk of infection without relying on commercial antibiotics. Biofilm-related infections are a class of notoriously difficult to treat healthcare-associated infections that frequently develop on the surface of implanted medical devices. As biofilm formation is a surface-associated phenomenon, understanding how the intrinsic properties of materials affect bacterial adhesion enables the development of structure-property relationships that can guide the future design of infection-resistant materials. Despite lacking visual, auditory, and olfactory perception, bacteria still manage to sense and attach to surfaces. Previously, it has been reported that bacteria can detect and differentiate the surface chemistry and topography of surfaces; however, the influence of the stiffness and thickness on bacterial-surface interactions remains unknown. In this thesis, the effect that the fundamental material properties of polymer films and hydrogels (stiffness, thickness, and chemistry) have on the adhesion and surface-associated transport of bacteria was investigated. By decoupling the effect of the hydrogel’s stiffness and thickness from their chemistry, we suggest a key takeaway design rule: to optimize fouling-resistance, hydrogel coatings should be thick and soft. Two chemically distinct hydrogels, poly(ethylene glycol) and agar, were synthesized over a 1-1000 kPa range of Young’s modulus. Static adhesion experiments, conducted on 150 µm thick hydrogels, determined that Escherichia coli and Staphylococcus aureus colony surface coverage correlated positively with an increase in Young’s modulus. Notably, a substantial increase in adhesion occurred for both bacteria when the thickness of the hydrogels was reduced to 10 µm. The stiffness of poly(ethylene glycol) brushes and hydrogels was also found to influence the length and frequency of Staphylococcus aureus surface-associated transport via dynamic shear flow experiments. Furthermore, a universal hydrogel functionalization platform was developed for instances where mechanical properties of hydrogels are not adjustable. The incorporation of the fouling-resistant polymer zwitterion, poly(2-methacryloyloxyethyl phosphorylcholine), enhanced resistance to bacterial adhesion without altering the mechanical properties of covalently or physically crosslinked hydrogels. This thesis demonstrates that by combining structure-property relationships with fouling-resistant zwitterionic chemistry, the adhesion of proteins and microorganisms to polymer hydrogels is reduced.