Withstanding high pressures in polymeric microchannels is an important requirement for many biological applications. Here, a simple direct polymerization through a polyester photomask is applied to obtain monolithic polyethylene glycol (PEG)-modified poly(methyl methacrylate) (PMMA) (PEGMA) microchannels, showing the ability to withstand pressure up to 12 MPa in burst pressure tests. The ability of withstanding high pressures is observed to increase with increasing ratio between the thickness of the cover polymer layer forming the microchannel lid and the width of the microchannel. A simplified finite element modeling model of the burst pressure test is set up to interpret the experimental findings. The outcomes of the modeling activity, along with direct scanning electron microscopy observation of the fracture surfaces, confirm the effectiveness of the polymerization method for the production of monolithic PEGMA microchannels. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41031.