The purpose of the present case report study was to clinically and histologically evaluate the healing of deep intrabony defects following treatment with either a combination of an enamel matrix protein derivative (EMD) and a bovine-derived xenograft (BDX) or with BDX alone. Three female patients with generalized marginal periodontitis and presenting one advanced intrabony defect each were treated with either a combination of EMD + BDX (two defects) or with BDX alone (one defect). The postoperative healing was uneventful in all three cases. Six months after surgery, a gain of clinical attachment was measured at all treated sites. The histologic examination revealed that all three defects healed with a new connective tissue attachment (ie, new cellular cementum with inserting collagen fibers) and new bone. Most of the BDX particles were surrounded by a bone-like tissue. No direct contact between BDX particles and the root surface (cementum or dentin) was observed. Within their limits, the present data indicate that treatment with either EMD + BDX or with BDX alone may enhance the formation of new connective tissue attachment and new bone in human intrabony defects.