BACKGROUND Regenerative periodontal surgery utilizing a combination of an enamel matrix protein derivative (EMD) and a natural bone mineral (NBM) and platelet-rich plasma (PRP) has been shown to enhance the outcomes of regenerative surgery significantly. At present, it is unknown whether root conditioning with EMD, followed by defect fill with a combination of NBM+PRP may additionally enhance the clinical results obtained with EMD+NBM. OBJECTIVE To compare clinically the treatment of deep intrabony defects with either EMD+NBM+PRP or EMD+NBM. METHODS Twenty-six patients suffering from advanced chronic periodontitis, and each of whom displayed one advanced intrabony defect were randomly treated with either EMD+NBM+PRP (test) or EMD+NBM (control). The following clinical parameters were evaluated at baseline and at 1 year after treatment: plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR) and clinical attachment level (CAL). The primary outcome variable was CAL. RESULTS Healing was uneventful in all patients. At 1 year after therapy, the test sites showed a reduction in mean PD from 8.8+/-1.9 mm to 3.1+/-0.9 mm ( p<0.001) and a change in mean CAL from 10.8+/-2.0 mm to 6.0+/-1.5 mm ( p<0.001). In the control group the mean PD was reduced from 8.8+/-2.0 mm to 2.8+/-1.6 mm ( p<0.001) and the mean CAL changed from 10.5+/-1.6 mm to 5.5+/-1.4 mm ( p<0.001). CAL gains of > or =4 mm were measured in 77% (i.e. in 10 out of 13 defects) of the cases treated with EMD+NBM+PRP and in 100% (i.e. in all 13 defects) treated with EMD+NBM. No statistically significant differences in any of the investigated parameters were observed between the two groups. CONCLUSIONS Within its limits, the present study has shown that (i) 1 year after regenerative surgery, both treatments resulted in statistically significant PD reductions and CAL gains and (ii) the use of PRP failed to enhance the results obtained with EMD+NBM.