Sum frequency generation vibrational spectroscopy was applied to study the surface hydration and protein adsorption behavior on several polymer coatings based on pyridine, imidazole, and amine side groups along with vinyl or methacrylate backbones and their corresponding zwitterionic forms with carboxybetaine or sulfobetaine side chains, prepared by initiated chemical vapor deposition (iCVD). iCVD also enables facile tuning of the cross-linking density of the polymer coatings by blending in a cross-linker during the deposition, namely, 1,3,5,7-tetramethyl-1,3,5,7-tetravinyl cyclotetrasiloxane. Our results show that both the low- and high-cross-linking density zwitterionic polymers exhibit significantly better antifouling activities compared to those of the polymers without the zwitterionic side chains. The weak hydration signals from the low-density zwitterionic polymer/water interfaces were caused by the permeation of the polymer layer by water. The iCVD method is a widely applicable methodology to prepare zwitterionic polymer coatings with an excellent antifouling property.