Objective: The aim of the present study was to compare efficacy of nano-crystalline  and micro-crystalline forms of calcium sulfate bone grafts in the treatment of the periodontal intrabony defect. Methods: a total of 25 periodontal intarbony defect from nine patients were included in this study. The defect sites were randomly allocated in to two groups. Group I,  12 intrabony defect which treated by surgical periodontal flap and filled by nanocrystalline calcium sulfate bone graft. Group II,  13intrabony defect which treated by surgical periodontal flap and filled by microcrystalline calcium sulfate bone graft. Periodontal parameters (pocket depth, clinical attachment loss, gingival bleeding index and plaque index) were recorded at baseline and 3 months after surgery.  Results: Periodontal parameters, pocket depth, clinical attachment loss, gingival bleeding index and plaque index showed no significant d iffwerence between the two studied group adter 3 months of surgery.  However, clinical attachment level gain showed significantly higher in nanocrystalline group compared to microcrystalline group after 3 months of surgery. Conclusion: Both nanocrystalline calcium sulfate  and  microcrystalline form of calcium sulfate have similar efficacy on the outcome improvement in surgical treatment of the periodontal intrabony defect at short period interval (3 months). Keywords.calcium sulfate, periodontal regeneration, intrbony defect, Nanostructured calcium sulfate.