Antifouling thin films of polyN,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl)-co-2-(dimethylamino)ethyl methacrylate-co-ethylene glycol dimethacrylate (PDDE) were synthesized via a substrate-independent and all-dry-initiated chemical vapor deposition (iCVD) technique followed by a diffusion-limited vapor-phase reaction with 1,3-propane sultone. Coated surfaces exhibited very low absorption of various foulants including bovine serum albumin (BSA), humic acid (HA), and sodium alginate (SA), as measured with the quartz crystal microbalance with dissipation monitoring (QCM-D). The fouling by humic acid was dependent on the presence of divalent cations such as Ca2+. Both depth profiling and angle-resolved X-ray photoelectron spectroscopy (XPS) measurements indicated that the zwitterionic groups were highly concentrated in the top ∼3 nm of the film. The contact angle measurements revealed a limited degree of surface chain reorganization upon contacting water. The dynamic contact angles remained unchanged after 100 days of storage in air, indicating the stability of the interface. The coating was substrate-independent, and the film was conformal on surface nanostructures including trenches, reverse osmosis membranes, and electrospun nanofiber mats.