The purposes of the present study were to explore the surgical possibilities for replacement of the medial tibial plateau by a metallic implant in a large animal model and to examine the implications for the opposing cartilage. In six goats, the medial tibial plateau of the right knee was replaced by a cobalt-chromium implant, using polymethylmethacrylate bone cement for fixation. The unoperated left knee served as a control. At 26 weeks after surgery, the animals were killed, and the joints evaluated macroscopically. Cartilage quality was analyzed macroscopically and histologically. Glycosaminoglycan content, synthesis, and release were measured in tissue and medium. All animals were able to move and load the knees without any limitations. Macroscopic articular evaluation scores showed worsening 26 weeks after inserting the implant (p < 0.05). Macroscopic and histologic scores showed more cartilage degeneration of the opposing medial femoral condyle in the experimental knee compared to the control knee (p < 0.05). Higher glycosaminoglycan synthesis was measured at the medial femoral condyle cartilage in the experimental knees (p < 0.05). This study shows that the medial tibial plateau can be successfully replaced by a cobalt-chromium implant in a large animal model. However, considerable femoral cartilage degeneration of the medial femoral condyle was induced, suggesting that care must be taken introducing hemiarthroplasty devices in a human clinical setting for the treatment of postmeniscectomy cartilage degeneration of the medial tibial plateau.