To isolate the primary variables influencing acetabular cup and interface stresses, we performed an evaluation of cup loading and cup support variables, using a Statistical Design of Experiments (SDOE) approach. We developed three-dimensional finite element (FEM) models of the pelvis and adjacent bone. Cup support variables included fixation mechanism (cemented or noncemented), amount of bone support, and presence of metal backing. Cup loading variables included head size and cup thickness, cup/head friction, and conformity between the cup and head. Interaction between and among variables was determined using SDOE techniques. Of the variables tested, conformity, head size, and backing emerged as significant influences on stresses. Since initially nonconforming surfaces would be expected to wear into conforming surfaces, conformity is not expected to be a clinically significant variable. This indicates that head size should be tightly toleranced during manufacturing, and that small changes in head size can have a disproportionate influence on the stress environment. In addition, attention should be paid to the use of nonmetal backed cups, in limiting cup/bone interface stresses. No combination of secondary variables could compensate for, or override the effect of, the primary variables. Based on the results using the SDOE approach, adaptive FEM models simulating the wear process may be able to limit their parameters to head size and cup backing.