Introduction: Endodontic post-treatment pain continues to be a significant problem facing the dental profession.Aim: This study is a triple blind study that evaluates the effect of prednisolone as a premedication in controlling post endodontic pain after single visit treatment of acute irreversible pulpitis using rotary system.Materials & Methods: Forty patients with irreversible pulpitis ready for root canal treatment were randomly assigned to 2 groups; prednisolone group (40 mg) and placebo group. The medications were given 30 minutes before the start of treatment. Root canal treatments were done using the Revo-S system in a single visit. Postendodontic pain was assessed after 6, 12, and 24 hours by using a visual analogue scale.Results: The outcome showed that prednisolone resulted in a statistically significant reduction in postendodontic pain at 6 and 12 hours. At 24 hours post operatively there was no significant difference between prednisolone and placebo in the management of post-endodontic pain. No side effects were reported for any of the medications used.Conclusions: This study suggests that a preoperative single oral dose of prednisolone could significantly reduce post-treatment endodontic pain in cases with acute irreversible pulpitis.