Trabecular bone, a porous, cellular type of bone found at the ends of the long bones and within the vertebrae, is subject to cyclic compressive loading resulting from the activities of daily living. Such fatigue loading can result in fracture, especially in vertebrae of patients with osteoporosis. As an initial step in understanding compressive fatigue of trabecular bone we previously used finite-element analysis to model the progressive damage and failure of a simple, two-dimensional hexagonal honeycomb. In this study, the analysis is extended to a random, Voronoi honeycomb. Bending of the cell walls induces tensile stresses even when the overall loading is compressive. The cell walls are assumed to have a distribution of crack lengths in their tensile zones. The cracks are assumed to grow according to a Paris law and fail when the cracks reach 75% of the cell wall thickness. Failed cell walls are removed from the structure, the stress distribution recalculated and the next increment of fatigue loading are simulated. The Young's modulus of the honeycomb is calculated after each cell wall failure. Overall failure of the Voronoi structure is assumed to occur when the modulus is reduced by 5%; further loading reduces the modulus sharply. The slope of the S-N curve for the Voronoi honeycomb is the same as that for the hexagonal honeycomb. The model suggests that a random honeycomb is more sensitive to fatigue than a regular one.