Friction and wear of four common orthopaedic biomaterials, alumina (Al2 O3 ), cobalt-chromium (CoCr), stainless steel (SS), and crosslinked ultra-high-molecular-weight polyethylene (UHMWPE), sliding against bovine articular cartilage explants were investigated by reciprocating sliding, nanoscale friction and roughness measurements, protein wear assays, and histology. Under the experimental conditions of the present study, CoCr yielded the largest increase in cartilage friction coefficient, largest amount of protein loss, and greatest change in nanoscale friction after sliding against cartilage. UHMWPE showed the lowest cartilage friction coefficient, least amount of protein loss, and insignificant changes in nanoscale friction after sliding. Although the results are specific to the testing protocol and surface roughness of the examined biomaterials, they indicate that CoCr tends to accelerate wear of cartilage, whereas the UHMWPE shows the best performance against cartilage. This study also shows that the surface characteristics of all biomaterials must be further improved to achieve the low friction coefficient of the cartilage/cartilage interface.