The treatment of chondral defects using microdrilling often results in a mechanically weak fibrocartilagenous repair, rather than a more robust hyaline cartilage repair. Many different microfracture/microdrilling augmentation techniques have been described, including the use of cellular products to enhance healing. Autologous peripheral blood progenitor cells can be obtained via apheresis after administration of granulocyte colony-stimulating factor (G-CSF) and have been used successfully to augment microdrilling in clinical patients. The objective of this study was to use apheresis-derived mononuclear blood cells to augment microdrilling treatment of a cartilage defect in an ovine model to determine the effect on healing. Forty adult female sheep were used in this study and were divided into a control group (microdrilling alone) and a treatment group (microdrilling, hyaluronic acid, and apheretic product). Outcome measurements included weight-bearing on the operated limb, macroscopic scoring of the joint, histology, and immunohistochemistry. In addition, magnetic resonance imaging was used to attempt to identify SPION-labeled cells from the apheretic product in the operated limbs. The results showed a significant increase in healing as measured by the modified O'Driscoll sore in the treated group. No evidence of homing of SPION-labeled cells to the defect was found and no correlation was found between the response to G-CSF administration or concentration of CD34+  and outcome. A correlation was found between healing and the concentration of white blood cells and peripheral blood mononuclear cell numbers in the apheretic product.