The purpose of the present study was to compare the treatment of deep intrabony defects with a combination of an enamel matrix protein derivative (EMD; Emdogain) and a bovine-derived xenograft (BDX; Bio-Oss) to BDX alone. Twenty-four healthy patients, each of whom displayed one intrabony defect, were randomly treated with a combination of EMD + BDX (test) or with BDX alone (control). Soft tissue measurements were made at baseline and 1 year following the therapy. No differences in any of the investigated parameters were observed at baseline between the two groups. No adverse healing response was observed in any of the patients. At 1 year after therapy, the sites treated with EMD + BDX showed a reduction in probing pocket depth (PPD) from 10.0 ± 1.5 mm to 4.3 ± 1.4 mm and a change in clinical attachment level (CAL) from 10.9 ± 2.0 mm to 6.2 ± 1.9 mm (P .0001). In the group treated with BDX, the PPD was reduced from 9.7 ± 2.4 mm to 3.2 ± 0.7 mm and the CAL changed from 10.1 ± 2.3 mm to 5.2 ± 1.2 mm (P .0001). Hard tissue fill was observed radiographically in all defects. Both treatments resulted in significant improvements of PPD and CAL. However, no statistically significant differences in any of the investigated parameters were observed between the test and control groups. Both therapies led to significant improvements of the investigated clinical parameters.