We have demonstrated that molecularly engineering the chemical structure of a monomer can lead to hydrogels with improved mechanical strength. In this case, hydrogels from zwitterionic sulfobetaine methacrylate monomers were compared to sulfobetaine vinylimidazole (pSBVI) hydrogels. We show that the introduction of the vinylimidazole backbone improves the tensile and compressive mechanical properties of the sulfobetaine hydrogel by an order of magnitude over the same properties of a methacrylate hydrogel. Zwitterionic groups have been shown to create surface coating materials with ultralow fouling properties, and we demonstrate here that the presence of the imidazole group does not compromise the nonfouling properties attributed to the zwitterionic sulfobetaine: surfaces coated with pSBVI exhibited exceptionally low nonspecific protein adsorption, and cell adhesion was reduced by 97% relative to low-fouling poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels.