Fatigue cracking in the cement mantle of total hip replacement has been identified as a possible cause of implant loosening. Retrieval studies and in vitro tests have found porosity in the cement may facilitate fatigue cracking of the mantle. The fatigue process has been simulated computationally using a finite element/continuum damage mechanics (FE/CDM) method and used as a preclinical testing tool, but has not considered the effects of porosity. In this study, experimental tensile and four-point bend fatigue tests were performed. The tensile fatigue S-N data were used to drive the computational simulation (FE/CDM) of fatigue in finite element models of the tensile and four-point bend specimens. Porosity was simulated in the finite element models according to the theory of elasticity and using Monte Carlo methods. The computational fatigue simulations generated variability in the fatigue life at any given stress level, due to each model having a unique porosity distribution. The fracture site also varied between specimens. Experimental validation was achieved for four-point bend loading, but only when porosity was included. This demonstrates that the computational simulation of fatigue, driven by uniaxial S-N data can be used to simulate nonuniaxial loadcases. Further simulations of bone cement fatigue should include porosity to better represent the realities of experimental models.