BACKGROUND: Odontogenic cysts with large bony defects have always been the drawback for conservative management of these lesions. The healing of bony defects with bone regeneration of bone in cystic cavities has always been a challenging task. Various bone substitutes have been used to accelerate bone formation in cystic cavities. The greatest drawback of alloplasts is lack of osteogenic or osteoconductive property. This has led to a severe attempt to improve the physical properties of alloplastic materials by combining molecular, cellular and genetic tissue engineering technologies and one such attempt is platelet rich fibrin(PRF). The purpose of this study is to assess the healing of bone defects following cyst enucleation when osteoconductive alloplasts are combined with PRF. MATERIALS AND METHODS: This single group randomized interventional study was done on 20 patients (14 male and 6 female) in the age group of 18 to 50 years. Patients with Mandibular or Maxillary odontogenic cysts with radiographic radiolucency measuring upto 5 cm in any of the three dimensions, and who were willing for a regular follow up were included. The enucleated cystic bony cavities were filled with autogenous PRF and alloplastic bone graft material. The patients were followed up for a period of two years. The bone formation in the cystic cavity was assessed preoperatively and post operatively using Orthopantomogram (OPG). The density of the bone formed post operatively was assessed using Computed Tomography (CT) scan after 6 months and was compared with the normal bone on the opposite side in Hounsefield units(HU). Infection and wound dehiscence were also assessed. RESULTS AND CONCLUSIONS: The mean age group of the patients were 29.9 ± 8.15 years. 60% of the odontogenic cysts were found in the anterior region from canine to canine. Histopathologic diagnosis of treated cysts revealed 70% were radicular cysts and 30% were dentigerous cysts. The average dimensions of the cyst measured from the CT scan was: supero inferiorly 1.17 ± 0.41 cm, antero posteriorly 1.495 ± 0.86 cm, and medio lateral dimension 2.17 ± 0.75 cm. The average bone density in the cystic cavity filled with bone graft mixed with autogenous PRF achieved after six months was 374.35 ± 38.786 HU which was significantly higher than the average bone density on the contra lateral side (normal bone) which was 315.279 ± 43.476 HU.