Introduction. Unicompartmental arthroplasty of the knee in patients with isolated medial osteoarthritis gives good results, but survival is inferior to that of total knee prosthesis. Knees may fail because positioning of the prosthesis has been suboptimal. The aim of this study was to investigate the influence of the tibial slope on the rate of wear of a medial fixed-bearing unicompartmental knee arthroplasty. Materials and Methods. We simulated wear on a medial fixed-bearing unicompartmental knee prosthesis (Univation) in vitro with a customised, four-station, and servohydraulic knee wear simulator, which exactly reproduced the walking cycle (International Organisation for Standardisation (ISO) 14243-1:2002(E)). The medial prostheses were inserted with 3 different posterior tibial slopes: 0°, 4°, and 8° (n = 3 in each group). Results. The wear rate decreased significantly between 0° and 4° slope from 10.4 (SD 0.62) mg/million cycles to 3.22 (SD 1.71) mg/million cycles. Increasing the tibial slope to 8° did not significantly change the wear rate. Discussion. As an increase in the tibial slope reduced the wear rate in a fixed-bearing prosthesis, a higher tibial slope should be recommended. However, other factors that are influenced by the tibial slope (e.g., the tension of the ligament) must also be considered.