To gain insight into how the pressure drop in monolithic silica columns is determined by the microscopic details of the pore structure, a series of well-validated computational fluid dynamics simulations has been performed on a simplified model structure, the so-called tetrahedral skeleton column. From these simulations, a direct correlation between the pressure drop and two main structural properties (skeleton thickness and column porosity) of the monolithic skeleton could be established. The correlation shows good agreement with the experimental pressure-drop data available from the literature on silica monoliths, especially when a correction for the flow-through pore size heterogeneity is made. The established correlation also yields a much more accurate representation of the relation between the flow resistance and the bed porosity than does the Kozeny-Carman model, making it much better suited for porosity optimization calculations.