Aseptic loosening is the most common reason for long-term revision of total joint replacement (TJR). Infection is the main reason for short-term revision of TJR. In our previous studies, experimental results showed that acrylic bone cement-loaded with antibiotics had a detrimental effect on cement strength such as bending strength, compressive strength, and fracture toughness. This result implied that the mechanical failure of antibiotic loaded bone cement was potentially related to porosity volume fraction. Hence, the objective of this study was to investigate the effect of pore size and distribution on bone cement fracture toughness. The effect of pores was analyzed using the extended Finite Element Method (X-FEM) method to model crack propagation and its modulation by pore sizes and locations. Numerically obtained load-displacement responses were compared to experimental results. We observed that crack propagation is affected by several pore parameters; as expected these include pore size and pore locations (pore-pore interactions) and are related to implicit pore-crack interactions. The experimental and numerical investigations presented in the current study contribute to a better understanding of the effect of pores on bone cement fracture toughness; key insights include the identification of a critical pore size for reduced fracture toughness, and relative insensitivity of crack propagation to stochastically distributed pore locations.