Bone replacement grafts (BRG) are widely used in the treatment of periodontal osseous defects; however, the clinical benefits of this therapeutic practice require further clarification through a systematic review of randomized controlled studies. The purpose of this systematic review is to access the efficacy of bone replacement grafts in proving demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone. What is the effect of bone replacement grafts compared to other interventions on clinical, radiographic, adverse, and patient-centered outcomes in patients with periodontal osseous defects? The computerized bibliographical databases MEDLINE and EMBASE were searched from 1966 and 1974, respectively, to October 2002 for randomized controlled studies in which bone replacement grafts were compared to other surgical interventions in the treatment of periodontal osseous defects. The search strategy included screening of review articles and reference lists of retrieved articles as well as hand searches of selected journals. All searches were limited to human studies in English language publications. Non-randomized observational studies (e.g., case reports, case series), publications providing summary statistics without variance estimates or data to permit computation, and studies without BRG intervention alone were excluded. The therapeutic endpoints examined included changes in bone level, clinical attachment level, probing depth, gingival recession, and crestal resorption. For purposes of meta-analysis, change in bone level (bone fill) was used as the primary outcome measure, measured upon surgical re-entry or transgingival probing (sounding). 1. Forty-nine controlled studies met eligibility criteria and provided clinical outcome data on intrabony defects following grafting procedures. 2. Seventeen studies provided clinical outcome data on BRG materials for the treatment of furcation defects. 1. With respect to the treatment of intrabony defects, the results of meta-analysis supported the following conclusions: 1) bone grafts increase bone level, reduce crestal bone loss, increase clinical attachment level, and reduce probing depth compared to open flap debridement (OFD) procedures; 2) No differences in clinical outcome measures emerge between particulate bone allograft and calcium phosphate (hydroxyapatite) ceramic grafts; and 3) bone grafts in combination with barrier membranes increase clinical attachment level and reduce probing depth compared to graft alone. 2. With respect to the treatment of furcation defects, 15 controlled studies provided data on clinical outcomes. Insufficient studies of comparable design were available to submit data to meta-analysis. Nonetheless, outcome data from these studies generally indicated positive clinical benefits with the use of grafts in the treatment of Class II furcations. 3. With respect to histological outcome parameters, 2 randomized controlled studies provide evidence that demineralized freeze-dried bone allograft (DFDBA) supports the formation of a new attachment apparatus in intrabony defects, whereas OFD results in periodontal repair characterized primarily by the formation of a long junctional epithelial attachment. Multiple observational studies provide consistent histological evidence that autogenous and demineralized allogeneic bone grafts support the formation of new attachment. Limited data also suggest that xenogenic bone grafts can support the formation of a new attachment apparatus. In contrast, essentially all available data indicate that alloplastic grafts support periodontal repair rather than regeneration. 4. The results of this systematic review indicate that bone replacement grafts provide demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone.