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Background: This randomized controlled clinical trial compared the effects of platelet-rich fibrin (PRF) and concentrated growth factor (CGF) on early bone healing after endodontic microsurgery. Methods: Eighteen patients with an isolated periapical lesion < 10 mm in the maxillary anterior region were randomly assigned to three groups: control, PRF, or CGF. Endodontic microsurgery was performed and PRF or CGF membranes were placed over the bone defects in the experimental groups. The volume of the bone defect at postoperative one week, three months, and six months was evaluated using cone-beam computed tomography and Mimics software. The results were statistically analyzed using the Kruskal–Wallis test and post-hoc Mann–Whitney U test with Bonferroni correction. Results: At the three-month follow-up, the PRF and CGF groups showed significantly greater bone healing compared with the control group (p > 0.05). However, no significant difference was observed between the PRF and CGF groups. At the six-month follow-up, no significant differences were observed between the groups. Conclusions: These results suggested that PRF and CGF promote early bone healing after endodontic microsurgery. [ABSTRACT FROM AUTHOR] more...