Background. The purpose of this study was to evaluate the combination of an enamel matrix derivative (EMD) and an osteoconductive bone ceramic (BC) in improving bone regeneration. Materials and Methods. Four cylindrical cavities (6 × 6 mm) were prepared bilaterally in the mandible in three dogs. The defects were randomly assigned to four different treatments—filled with EMD/BC and covered with a nonresorbable membrane, filled with EMD/BC without membrane, membrane coverage only, or control (left untreated)—and healed for 2, 4, or 6 weeks. Harvested specimens were prepared for histologic, histomorphometric, and immunohistochemical analyses. Results. Sites treated with EMD/BC with or without membrane showed more total bone formation and lamellar bone formation than membrane-only and control defects. There were no statistically significant differences in total bone formation between EMD/BC with or without membrane. Conclusion. EMD with BC might improve bone formation in osseous defects more than membrane coverage alone; the use of a membrane had no significant additive effect on total bone formation.