Unicompartmental knee arthroplasty (UKA) has become a standard procedure with good clinical outcome in patients with isolated medial osteoarthritis of the knee. However, the survival rates of UKA are still inferior compared to that of total knee arthroplasty. Aseptic loosening and wear are responsible for more than 50% of revisions. Therefore, this study evaluated the influence of the tibial slope on the wear rate in a medial UKA. The wear rate of a medial mobile-bearing UKA (Univation® Aesculap, Tuttlingen, Deutschland) was evaluated according to the ISO 14243-1:2002(E) norm with a customized four-station servo-hydraulic knee wear simulator (EndoLab, Thansau, Germany). In the first group, the prostheses was medially implanted with 0° slope (n = 3) and in the second group the prostheses was medially implanted with 8° slope (n = 3). The lateral side was kept constant with 0° in both groups. For each implant, a total of 5.0 million cycles was performed and after every 0.5 million cycles the gravimetric wear rate was determined. The wear rate in the 0° slope group was 3.46 ± 0.59 mg/million cycles and therefore significantly higher than in the 8° slope group with 0.99 ± 0.42 mg/million cycles (p < 0.01). An increase in the tibial slope leads to a reduced wear rate in a mobile-bearing UKA. Therefore, at least for this mobile-bearing UKA a higher tibial slope seems favorable to reduce the wear. However, before an optimal position of the tibial slope can be recommended, further investigations are required to evaluate the influence of the tibial slope on other factors, such as the ligament tension or the strain on the lateral compartment.