The purpose of this study was to compare the repair response of bioactive glass synthetic bone graft particles and open debridement in the treatment of human periodontal osseous defects. Fifty-nine defects in 16 healthy adults were selected. Each patient had at least 2 sites with attachment loss of at least 6 mm with clinical and radiographic evidence of intrabony or furcation defects. One to 3 months after cause-related therapy (oral hygiene instructions, scaling and root planing), the following measurements were recorded prior to surgery: probing depths, clinical attachment level, and gingival recession. Each defect was surgically exposed and measurements made of the alveolar crest height and base of osseous defect. The test defects were implanted with bioactive glass. The other sites served as unimplanted controls. Flaps were sutured at or close to the presurgical level. Radiographs and soft tissue presurgical measurements were repeated at 6, 9, and 12 months. At 12 months all sites were surgically re-entered to record osseous measurements. At the 12-month evaluation, significantly greater mean probing depth reduction was noted in the bioactive glass group compared to the controls (4.26 mm versus 3.44 mm; P = 0.028). Clinical attachment level gain was significantly improved (P = 0.0004) in the bioactive glass sites (2.96 mm) compared to the control sites (1.54 mm). There was significantly less gingival recession in the bioactive glass sites (1.29 mm) compared to the control sites (1.87 mm). Defect fill was significantly greater in the bioactive glass sites (3.28 mm) compared to the control sites (1.45 mm). Defect depth reduction was significantly greater in the bioactive glass sites (4.36 mm) compared to the control sites (3.15 mm). In conclusion, bioactive glass showed significant improvement in clinical parameters compared to open flap debridement.