BACKGROUND The aim of this study was to compare the clinical outcome of intrabony periodontal defects following treatment with a novel nanocrystalline hydroxyapatite (NHA) paste to open flap debridement. METHODS Twenty-eight subjects, each displaying one intrabony defect with probing depth (PD) > or =6 mm and radiographic evidence of an intraosseous component > or =3 mm participated in the present study. Subjects were allocated randomly to treatment with NHA paste (test group) or open flap debridement (control group). At baseline and at 6 months after surgery, the following clinical parameters were recorded by a masked examiner: plaque index, gingival index, PD, clinical attachment level (CAL), and gingival recession. RESULTS A significant improvement in PD and CAL was observed at 6 months after surgery compared to baseline in both treatment groups (P <0.001). At 6 months following therapy, the test group showed a reduction in mean PD from 7.4 +/- 1.3 mm to 3.4 +/- 1.2 mm and a change in mean CAL from 8.0 +/- 1.3 mm to 4.4 +/- 1.7 mm, whereas in the control group the mean PD decreased from 7.4 +/- 0.8 mm to 4.9 +/- 0.9 mm, and mean CAL decreased from 8.1 +/- 1.2 mm to 6.4 +/- 1.3 mm. The intergroup comparison demonstrated significantly more PD reductions (P = 0.012) and CAL gains (P = 0.005) in the test group compared to the control group. CONCLUSIONS Treatment of intrabony periodontal defects with NHA paste significantly improved clinical outcomes compared to open flap debridement.