Beginning in the 1970s, device retrieval analysis was conducted at our institution, the University of Alabama at Birmingham, to better understand surgical implant device biocompatibilities through studies of element (biomaterial) and force (biomechanical) transfers at host-device interfaces. Multidisciplinary investigations were initiated from analyses of clinical outcomes and examination of explants. Analyses included physical, mechanical, chemical, electrical, and combinations thereof for orthopedic and dental implants fabricated from synthetic origin biomaterials, with more than 8,000 specimens received. Hypotheses were tested concerning cause-effect relationships using a tiered classification approach, which resulted in peer-reviewed presentations and publications (STP1560, Metal-on-Metal Total Hip Replacement, and STP1591, Modularity and Tapers in Total Joint Replacement Devices). In the 1990s, the focus evolved to include the analysis of function of implants obtained through postmortem retrieval, with more than 1,000 “en bloc” specimens collected. Opportunities included longer-term evaluations of human outcomes for devices that were in place and functional at the time of donation. Direct comparisons of devices and tissues with laboratory and in vivo studies tested theories about cause-effect relationships. Selected studies are presented as examples that include the application of calcium phosphate coatings, particulates and porous blocks for bone grafting with dental implants, and surface stability of a contemporary total knee replacement intended to reduce the generation of wear debris. We conclude with recommendations for expanded analysis of postmortem specimens by qualified investigators as input to new consensus standards.