The aim of this study was to evaluate the effect of Prednisolone as Premedication in reduction of post endodontic pain of acute irreversible pulpitis treated in a single visit using rotary system.Materials & Methods: In this study 40 patients with irreversible 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.Results: Results showed that there was a significant difference in the visual analogue scores between Prednisolone and Placebo groups at all intervals. Prednisolone made a statistically significant reduction in post endodontic pain at 6, 12 and 24 hours post operatively. There was also significant difference between Prednisolone and Placebo groups in developing the event of no 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.