OBJECTIVE: The objective of this study was to describe the mechanism of healing of osteochondral defects of the distal femur in the sheep, a commonly used translational model. Information on the healing mechanism be useful to inform the design of tissue engineering devices for joint surface defect repair. DESIGN: A retrospective study was conducted examining 7-mm diameter osteochondral defects made in the distal medial femoral condyle of 40 adult female sheep, comprising control animals from 3 separate structures. The healing of the defects was studied at post mortem at up to 26 weeks. RESULTS: Osteochondral defects of the distal femur of the sheep heal through endochondral ossification as evidenced by chondrocyte hypertrophy and type X collagen expression. Neocartilage is first formed adjacent to damaged cartilage and then streams over the damaged underlying bone before filling the defect from the base upward. No intramembranous ossification or isolated mesenchymal stem cell aggregates were detected in the healing tissue. No osseous hypertrophy was detected in the defects. CONCLUSIONS: Osteochondral defects of the medial femoral condyle of the sheep heal via endochondral ossification, with neocartilage first appearing adjacent to damaged cartilage. Unlike the mechanism of healing in fracture repair, neocartilage is eventually formed directly onto damaged bone. There was most variability between animals between 8 and 12 weeks postsurgery. These results should be considered when designing devices to promote defect healing.