Aim: The present study compared hydroxyapatite granules, CERAMENT™, and platelet-rich fibrin (PRF) in the management of endodontic apical surgery cases. Materials and methods: The present study was conducted on 126 patients requiring apical surgery of both genders. Patients were treated with hydroxyapatite granules, CERAMENT™, and PRF and were recalled regularly for assessment of pain, mobility, presence or absence of sinus, and healing site. Results: The mean days taken for the disappearance of pain in group I was 51.2 days, in group II was 52.3 days, and in group III was 44.7 days. The difference was significant (p < 0.05). There was a less number of draining sinuses in II and III groups. This was statistically significant (p < 0.05). Significantly less area remained after surgical intervention in groups II and III compared to group I recorded at follow-up period. The difference was significant (p < 0.05). Conclusion: Authors found PRF superior in terms of reducing pain, mobility, and sinus and improving the healing site as compared to hydroxyapatite and CERAMENT™. Clinical significance: Platelet-rich fibrin is considered more superior in terms of reducing pain, mobility, and sinus and improving the healing site, and it can be advised in clinical practice for endodontic management.