Immobilization of biomolecules, such as proteins or sugars, is a key issue in biotechnology because it enables the understanding of cellular behavior in more biological relevant environment. Here, poly(4-ethynyl-p-xylylene-co-p-xylylene) coatings have been fabricated by chemical vapor deposition (CVD) polymerization in order to bind bioactive molecules onto the surface of the material. The control of the thickness of the CVD films has been achieved by tuning the amount of precursor used for deposition. Copper-catalyzed Huisgen cycloaddition has then been performed via microcontact printing to immobilize various biomolecules on the reactive coatings. The selectivity of this click chemistry reaction has been confirmed by spatially controlled conjugation of fluorescent sugar recognizing molecules (lectins) as well as cell adhesion onto the peptide pattern. In addition, a microstructured coating that may undergo multiple click chemistry reactions has been developed by two sequential CVD steps. Poly(4-ethynyl-p-xylylene-co-p-xylylene) and poly(4-formyl-p-xylylene-co-p-xylylene) have been patterned via vapor-assisted micropatterning in replica structures (VAMPIR). A combination of Huisgen cycloaddition and carbonyl-hydrazide coupling was used to spatially direct the immobilization of sugars on a patterned substrate. This work opens new perspectives in tailoring microstructured, multireactive interfaces that can be decorated via bio-orthogonal chemistry for use as mimicking the biological environment of cells.