This clinical study was designed to evaluate the volumetric healing of periapical (PA) bone defect after PA surgery, using platelet-rich fibrin (PRF), and its combination with hydroxyapatite and alendronate.Twenty male patients of age between 25 and 35 years, having PA pathology (>5 mm on intraoral periapical radiograph (IOPA)) with intraoral sinus opening, were included in this study. Cone-beam computed tomography (CBCT) imaging of all patients was done. Root canal treatment with PA surgery was done. Patients were divided into four groups (5 in each group), on the basis of material placed in PA bone defect. After 1 year, CBCT imaging was done. Linear measurement of maximal dimensions in all three orthogonal planes was done in both pre- and post-CBCT image. These measurements were used to estimate the volume of the lesion healed after 1 year of surgery.Analysis of variance and Post hoc Tukey's test were used for statistical analysis.Change in volume were significantly different between Group 1 vs Group 3; Group 2 vs Group 3 and Group 3 vs Group 4. The Group Order for change in volume 1 year post surgery Group 3> Group 4 ≈ Group 2> Group 1.PA bone healing after surgery is enhanced by placing combination of bone regenerative materials. PRF with hydroxyapatite provides best healing outcomes in comparison to PRF with alendronate or PRF alone.