The present study clinically and histologically evaluated healing of human intrabony defects following treatment with a combination of enamel matrix derivative (EMD) and bioactive glass (BG) or BG alone. Six patients displaying either combined oneand two-walled (five patients) or three-walled (one patient) intrabony defects around teeth scheduled for extraction were included. A notch was placed at the most apical extent of the calculus on the root surface to serve as a reference. Six months after surgery, the teeth or roots were extracted, together with some of their surrounding soft and hard tissues, and processed for histologic evaluation; a gain of clinical attachment was found in all cases. Healing in all three defects treated with EMD + BG was mainly characterized by new cementum with inserting collagen fibers and new periodontal ligament; most graft particles were surrounded by bone-like tissue, indicating ongoing mineralization. Treatment with BG resulted in epithelial downgrowth and connective tissue encapsulation of the graft material in all three specimens. Reformation of cementum and periodontal ligament was observed in one of the specimens, limited to the most apical part of the defect. Formation of bone-like tissue around the graft particles was observed in only one of the three specimens treated with BG. Direct contact between the BG particles and root surface (cementum or dentin) was not observed in any of the six specimens. BG alone has low potential to facilitate periodontal regeneration. However, EMD + BG resulted in formation of new cementum with an associated periodontal ligament, as well as enhanced mineralization around the BG particles.