Defects of the meniscus greatly alter knee function and predispose the joint to degenerative changes. The purpose of this study was to test a recently developed cell-scaffold combination for the repair of a critical-size defect in the canine medial meniscus. A bilateral, complete resection of the anterior horn of the medial meniscus was performed in 18 Beagle canines. A PLGA scaffold was implanted into the defect of one knee of 6 canines and the contralateral defect was left untreated. Scaffolds loaded with autologous myoblasts and cultured in a chondrogenic medium for 14 days were implanted in a second series of 12 canines. Empty scaffolds were implanted in the contralateral knees. Menisci were harvested at 12 weeks. Untreated defects had a muted fibrous healing response. Defects treated with cell-free implants also showed predominantly fibrous tissue, whereas fibrocartilage was present in several scaffolds. The thickness of the repair tissue after treatment with cell-free scaffolds was significantly greater compared to the controls (p<0.05). Pre-cultured implants integrated with the host tissue, and 9 of 12 contained meniscus-like fibrocartilage when compared to 2 of the 12 controls (p<0.05). The thickness of the pre-cultured implant repair tissue was greater compared to the controls (p<0.05). This study demonstrates the repair of a critical size meniscal defect using a stem cell and scaffold-based tissue engineering approach.