Two possible mechanisms for the reaction of four halogenated (metha)acrylate-based molecules with Parylene [poly (paraxylylene)] during its chemical vapor deposition were proposed. The chemical reactivity of acrylate double bond with the paraxylylene biradical was calculated for all four (metha)acrylate-based molecules. These calculations allowed the evaluation of the energetically favorable mechanism and indeed a direct correlation was found between both predicted and experimental reactivities. Next, the reactivity of the (metha)acrylate-modified Parylene films was evaluated through their reaction with different amines. The obtained amidated Parylene films were characterized with X-ray photoelectron spectroscopy, Kaiser test for primary amines, and fluorescence microscopy. The strong reactivity of (metha)acrylate-modified Parylene films toward nucleophilic substitution emphasizes a general method for the functionalization of self-supported Parylene films grown on the reacting solutions using the novel solid on liquid deposition process. This paves the way to the development of multifunctional materials in a one-step process resulting from the deposition Parylene over liquid patterns. (C) 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: 2952-2958, 2011