The development of generally applicable protocols for the surface modification of complex substrates has emerged as one of the key challenges in biotechnology. The use of vapor-deposited polymer coatings may provide an appealing alternative to the currently employed arsenal of surface modification methods consisting mainly of wet-chemical approaches. Herein, we demonstrate the usefulness of chemical vapor deposition polymerization for surface modification in confined microgeometries with both nonfunctionalized and functionalized poly(p-xylylenes). For a diverse group of polymer coatings, homogeneous surface coverage of different microgeometries featuring aspect ratios as high as 37 has been demonstrated based on optical microscopy and imaging X-ray photoelectron spectroscopy. In addition, height profiles of deposited polymer footprints were obtained by atomic force microscopy and imaging ellipsometry indicating continuous transport and deposition throughout the entire microchannels. Finally, the ability of reactive coatings to support chemical binding of biological ligands, when deposited in previously assembled microchannels, is demonstrated, verifying the usefulness of the CVD coatings for applications in micro/nanofluidics, where surface modifications with stable and designable biointerfaces are essential. The fact that reactive coatings can be deposited within confined microenvironments exhibits an important step toward new device architectures with potential relevance to bioanalytical, medical, or "BioMEMS" applications.