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Aim: Numerous pulp-capping agents such as mineral trioxide aggregate (MTA), calcium hydroxide (Ca(OH)2), platelet-rich fibrin (PRF), and biodentine have been suggested. This clinical study was conducted to compare MTA, PRF, and Ca(OH)2 in teeth with irreversible pulpitis. Materials and Methods: The 60 mandibular molar teeth with irreversible pulpitis were used in this study, which were restored with Ca(OH)2, MTA, and PRF. Assessments of the treatment were carried out at 6 months and 1 year by clinical examination and also radiographically. Results: A nonsignificant difference was observed in pain intensity recorded at numerical rating scale at baseline, 24h, 1 week, 1 month, 3 months, 6 months, and 1 year. A nonsignificant (P > 0.05) difference was reported in clinical and radiographic success rate recorded at 6 months and 1 year in all groups. Conclusion: Pulp-capping agents such as Ca(OH)2, MTA, and PRF yielded similar success rate when used in teeth with irreversible pulpitis.