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The purpose of this study was to evaluate the ability of fibronectin to augment the regenerative effects of a bovine-derived xenograft in human periodontal defects. Using a parallel arm, randomized double-blind design, 24 patients with an intrabony defect or a Class II furcation defect were randomly assigned to either the experimental group (xenograft plus fibronectin) or the control group (xenograft without fibronectin). Probing attachment level, pocket depth, and gingival recession were measured at baseline and at 12 months after surgery. Both treatment modalities resulted in attachment gain and pocket depth reduction compared with baseline values. Changes in clinical attachment were not significantly different between the groups (gain of 1.5 mm ± 1.1 mm in the experimental group and 1.3 mm ± 1.4 mm in the control). Pocket depth reduction was greater in the control (2.3 mm ± 1.2 mm) than in the experimental group (2.1 mm ± 1.9 mm). Gingival recession also was greater in the control (0.9 mm ± 0.6 mm) than in the experimental group (0.6 ± 1.5 mm). Subtraction radiography revealed no significant differences between the groups when measuring changes in the distance between the cementoenamel junction and the crest of the bone or in the estimated gain in mineralized tissue mass. It was concluded that a significant difference between the regenerative treatment modalities could not be demonstrated within the limitations of the study. Fibronectin appears to have a stabilizing or proliferative effect on the gingival soft tissue by promoting less postoperative gingival recession.