The long-term stability of cemented total hip replacements critically depends on the lasting integrity of the bond between the cement and the bone, often referred to as fixation. In vitro assessment of fatigue behaviour of cemented acetabular, as opposed to femoral, replacements is of particular interest due to the more aggressive nature of late “loosening” found in acetabular replacements, reported to be three times that in femoral cases. Quantitative assessment of fatigue behaviour of cement fixation on acetabular side has been difficult due to the complexity of the pelvic bone geometry and the associated loading conditions.The purpose of this work was to develop a framework for in vitro assessment of fatigue integrity of cement fixation in acetabular replacements. To this end, a newly developed hip simulator was utilised, where the direction and the magnitude of the hip contact force (Bergmann et al., 2001) under typical physiological loading conditions including normal walking and stair climbing were simulated for the first time. Preliminary hip simulator experimental results seem to be consistent with those from constant amplitude fatigue tests, in that debonding at the bone–cement interface is identified as the main failure mechanism, although the numbers of cycles to failure are significantly reduced in samples tested in the hip simulator. Finite element analysis of implanted bone samples was carried out, where the effects of loading mode on the stress distribution in the cement mantle and at the bone–cement interface were evaluated. The effects of model geometry on the stress state and failure modes were also examined and discussed based on the results of the present and previously published work.