The wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial insert was determined using a four-station knee simulator. The bearings were subjected to flexion/extension (between 0 and 58 degrees ), anterior-posterior translation (between 0 and -5.2 mm), internal-external rotation (between -1.9 degrees and +5.7 degrees ), and a maximum axial load of 2.6 KN, as per ISO 14243-1,2,3. The wear tests were run at a frequency of 1.1 Hz for 5 million cycles, and the wear of the inserts (n = 3) was determined using the gravimetric method. The novelty of the study was a special setup developed to simulate, as realistically as possible, in vivo conditions; this involved fixing the femoral component to the distal end of a synthetic femur model by a qualified orthopedic surgeon using an approved method. After 5 million cycles, the mean weight losses were 11.16, 19.74, and 12.61 mg for specimens #1, #2, and #3, respectively. Visual and nondestructive inspections for each of the test specimens showed similar wear tracks and these were very similar to those seen on inserts retrieved after 2 years in vivo. These results show the efficacy of the new in vitro UHMWPE wear assessment method. Furthermore, a comparison between the present in vitro results and those reported in a relevant previous study provide some insight into the influence of the method used to fix the femoral component to the simulator on the wear magnitude and patterns of the tibial insert.