The aim of this study is to evaluate the effect of Prednisolone as Premedication in reduction of post endodontic pain of irreversible pulpitis treated in a single visit using rotary system. Materials and method; In this study 40 patients with irrivesrsible pulpitis undergoing root canal therapy were selected. Patients were randomly divided into two groups: Prednisolone group (A) and placebo group (B). Medication was given 30 minutes before start of the treatment. Root canal therapy was accomplished with Revo-S system in a single visit. Evaluation for the incidence of post-endodontic pain, using the visual analog scale approach 6, 12, 24, hours after the treatment was accomplished. Result; The results of this study indicated that oral administration of prednisolone in comparison with placebo at 6 and 12 hours periods significantly reduced post treatment endodontic pain. Conclusion; According to the above findings, oral administration of a single dose of prophylactic prednisolone could significantly reduce post treatment endodontic pain in cases with irreversible pulpitis.