BACKGROUND Alveolar bone loss and mobility of teeth is commonly observed in periodontitis patients. Regeneration of periodontal intrabony defects is indicated to restore the lost bone and periodontal tissues. The aim of the present study was to evaluate the clinical outcomes of periodontal intrabony lesions by using nanocrystalline hydroxyapatite (NHA) graft and comparing it with open flap debridement (OFD) alone. METHODS The eligibility criteria encompassed randomized (RCTs) and controlled clinical trials (CCTs). Weighted mean differences were calculated for clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction and gingival recession (REC) change, demonstrated as forest plots. The revised Cochrane Risk of Bias tool for randomized trials (RoB2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool were used for quality assessment of RCTs and non-randomized trials respectively. RESULTS From 22 full-text articles identified, three RCTs, one CCT and one retrospective follow-up of RCT were included. All the five papers comprised the quantitative evaluation. The use of NHA graft provided additional CAL gain of 0.96 mm (p = 0.0009) and PPD reduction of 0.97 mm (p < 0.00001) when compared to OFD alone. However, in terms of REC changes, no considerable benefits of NHA graft were demonstrated than OFD alone (p = 0.48). CONCLUSIONS The bioactive NHA graft showed promising results clinically in regenerative periodontology and can be considered for the management of periodontal intrabony defects. The use of NHA graft considerably provided better clinical outcomes in intrabony defects compared to using the OFD alone. Future research investigating NHA graft against other regenerative materials including specific BGs, at longer follow-up periods and bigger sample sizes and in furcation defects warranted.