Microposts are utilized to enhance heat transfer, adsorption/desorption, and surface chemical reactions. In a previous study [Yeom , J. Micromech. Microeng., 19, p. 065025 (2009)], based in part on an experimental study, an analytical expression was developed to predict the pressure drop across a microchannel filled with arrays of posts with the goal of fabricating more efficient micro-total analysis systems (µTAS) devices for a given pumping power. In particular, a key figure of merit for the design of micropost-filled reactors, based on the flow resistance models was reported thus providing engineers with a design rule to develop efficient µTAS devices. The study did not include the effects of the walls bounding the microposts. In this paper, a three-dimensional computational fluid dynamics model is used to include the effects of three-dimensionality brought about by the walls of the µTAS devices that bound the microposted structures. In addition, posts of smaller size that could not be fabricated for the experiments were also included. It is found that the two- and three-dimensional effects depend on values of the aspect ratio and the blockage ratios. The Reynolds number considered in the experiment that ranged from 1 to 10 was extended to 300 to help determine the range of Re for which the FOM model is applicable.