BACKGROUND: Regenerative periodontal therapy using platelet-rich plasma (PRP) and different types of bone substitutes with or without guided tissue regeneration (GTR) has been proposed as a modality to enhance the outcome of regenerative surgery. However, there are limited data from controlled clinical studies evaluating the effect of PRP on the healing of deep intrabony defects treated with a combination of bone substitutes and GTR. The aim of this study was to clinically evaluate the effect of PRP on the healing of deep intrabony defects treated with beta tricalcium phosphate (beta-TCP) and GTR by means of a non-bioresorbable expanded polytetrafluoroethylene membrane. METHODS: Twenty-eight subjects with advanced chronic periodontal disease and displaying one intrabony defect were treated randomly with a combination of PRP + beta-TCP + GTR or beta-TCP + GTR. Plaque index, gingival index, bleeding on probing, probing depth (PD), gingival recession, and clinical attachment level (CAL) were evaluated at baseline and at 1 year after treatment. CAL was the primary outcome variable. RESULTS: No differences in any of the investigated parameters were observed at baseline between the two groups. Healing was uneventful in all subjects. At 1 year after therapy, the sites treated with PRP + beta-TCP + GTR showed a reduction in mean PD from 9.1 +/- 0.6 mm to 3.3 +/- 0.5 mm (P <0.001) and a change in mean CAL from 10.1 +/- 1.3 mm to 5.7 +/- 1.1 mm (P <0.001). In the group treated with beta-TCP + GTR, mean PD was reduced from 9.0 +/- 0.8 mm to 3.6 +/- 0.9 mm (P <0.001), and the mean CAL changed from 9.9 +/- 1.0 mm to 5.9 +/- 1.2 mm (P <0.001). In both groups, all sites gained > or =3 mm of CAL. CAL gains > or =4 mm were noted in 86% (12 of 14 defects) of the cases treated with PRP + beta-TCP + GTR and in 79% (11 of 14 defects) of those treated with beta-TCP + GTR. No statistically significant differences in any of the investigated parameters were observed between the two groups at the 1-year reevaluation. CONCLUSION: At 1 year after surgery, both therapies resulted in significant PD reductions and CAL gains.