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 Prednisolone made a statistically significant reduction in postendodontic pain at 6 hours post operatively. At 12 and 24 hours post operatively there was no significant difference between Prednisolone and placebo in management of post endodontic pain. No side effects were reported for any of the medications used. In Placebo group there was a decrease in Visual Analogue Scale Score through follow up period and the difference was statistically significant. In Prednisolone group the change in Visual Analogue Scale Score was statistically non-significant. There was no significant difference between Prednisolone and Placebo groups in developing the event of no pain.Conclusion: Administration of a single preoperative oral dose of Prednisolone (40 mg) 30 minutes before start of treatment was effective in controlling post endodontic pain at 6 hours post operatively.