This research investigated the in-vitro wear and friction performance of polycarbonate urethane (PCU) 80A as they interact with articular cartilage, using a customised multidirectional pin-on-plate tester. Condyles were articulated against PCU 80A discs (Bionate® I and Bionate® II) (configuration 1) and the results arising from these tests were compared to those recorded during the sliding of PCU pins against cartilage plates (configuration 2). Configuration 1 produced steadily increasing coefficient of friction (COF) (up to 0.64 ± 0.05) and had the same trend as the cartilage–on–stainless steel articulation (positive control). When synovial fluid rather than bovine calf serum was used as lubricant, average COF significantly decreased from 0.50 ± 0.02–0.38 ± 0.06 for condyle–on–Bionate® I (80AI) and from 0.41 ± 0.02–0.24 ± 0.04 for condyle–on–Bionate® II (80AII) test configurations (p < 0.05). After 15 h testing, the cartilage–on–cartilage articulation (negative control) tests showed no cartilage degeneration. However, different levels of cartilage volume loss were found on the condyles from the positive control (12.5 ± 4.2 mm3) and the PCUs (20.1 ± 3.6 mm3 for 80 AI and 19.0 ± 2.3 mm3 for 80AII) (p > 0.05). A good correlation (R2 =0.84) was found between the levels of average COF and the volume of cartilage lost during testing; increasing wear was found at higher levels of COF. Configuration 2 showed low and constant COF values (0.04 ± 0.01), which were closer to the negative control (0.03 ± 0.01) and significantly lower than configuration 1 (p < 0.05). The investigation showed that PCU is a good candidate for use in hemiarthroplasty components, where only one of the two articulating surfaces is replaced, as long as the synthetic material is implanted in a region where migrating cartilage contact is achieved. Bionate® II showed better tribological performance, which suggests it is more favourable for use in hemiarthroplasty design.