A mini or partial arthroplasty may offer the advantages of reduced pain, shorter hospital stay, and increased range of motion, which are beneficial for the treatment of large-sized focal osteochondral defects. We aimed to evaluate the in vivo histologic response and function of our nonresorbable, composite structure implant, developed using polyetheretherketone (PEEK) and Ti6AI4V alloy, as a treatment for full-thickness osteochondral defects in the femoral head of the hip using a goat model. The gross and imaging appearance and histologic results were compared to those of a similar size cobalt-chromium-molybdenum (CoCrMo) alloy implant placed in a defect in the femoral head and evaluated up to 12 weeks. The X radiographs showed that there was no evidence of loosening of the implants for both the PEEK-Ti6AI4V and CoCrMo groups. Magnetic resonance imaging results showed no inflammatory signal findings in both PEEK-Ti6AI4V and CoCrMo implants. Macroscopically and histologically, there was lesser cartilage degeneration in the PEEK-Ti6AI4V implant than in the CoCrMo implant. The modified macroscopic articular evaluation score was lower in the PEEK-Ti6AI4V group than in the CoCrMo group (p < 0.05), and the histological score of the periprosthetic and acetabular cartilage was lower in the PEEK-Ti6AI4V group than in the CoCrMo group (P < 0.05). The micro-computed tomography results showed that the uncemented PEEK-Ti6AI4V implant has better osseointegration and higher bone-implant contact than the cemented CoCrMo implant. The peri-implant bone mass was higher in the PEEK-Ti6AI4V implant(p < 0.05). Meanwhile, the optical profile analytical results showed that the surface roughness of the cartilage in the acetabulum was higher in the CoCrMo group. In conclusion, the mini-arthroplasty implant based on PEEK-Ti6AI4V was superior to an identical CoCrMo alloy implant as a treatment for local osteochondral defect in the femoral head, owing to its in vivo cartilage protection and better osseointegration.