Orthopaedic implants experience large cyclic loads, and pre-clinical analysis is conducted to ensure they can withstand millions of loading cycles. Acetabular cup developments aim to reduce wall thickness to conserve bone, and this produces high pre-stress in modular implants. As part of an implant development process, we propose a technique for preclinical fatigue strength assessment of modular implants which accounts for this mean stress, stress concentrating features and material processing.A modular cup's stress distributions were predicted computationally, under assembly and in vivo loads, and its cyclic residual stress and stress amplitude were calculated. For verification against damage initiation in low-cycle-fatigue (LCF), the peak stress was compared to the material's yield strength. For verification against failure in high-cycle-fatigue (HCF) each element's reserve factor was calculated using the conservative Soderberg infinite life criterion.Results demonstrated the importance of accounting for mean stress. The cup was predicted to experience high cyclic mean stress with low magnitude stress amplitude: a low cyclic load ratio (Rl=0.1) produced a high cyclic stress ratio (Rs=0.80). Furthermore the locations of highest cyclic mean stress and stress amplitude did not coincide. The minimum predicted reserve factor Nf was 1.96 (HCF) and 2.08 (LCF). If mean stress were neglected or if the stress ratio were assumed to equal the load ratio, the reserve factor would be considerably lower, potentially leading to over-engineering, reducing bone conservation.Fatigue strength evaluation is only one step in a broader development process, which should involve a series of verifications with the full range of normal and traumatic physiological loading scenarios, with representative boundary conditions and a representative environment. This study presents and justifies a fatigue analysis methodology which could be applied in early stage development to a variety of modular and pre-stressed prosthesis concepts, and is particularly relevant as implant development aims to maximise modularity and bone conservation.