This study was designated to evaluate the effect of Prednisolone as premedication in controlling post-endodontic pain after single visit treatment of acute irreversible pulpitis using in a randomized controlled trial. 40 Mandibular Molar teeth were treated using Revo S system, Patients were asked To sign a printed consent and obligated the patient to fill the pain diary 6, 12, 24 hours after root canal treatment. The patients were randomly divided into 2 groups: experimental group (A) : prednisolone 40 mg and control group (B) : placebo. The pain was measured using VAS measurement, a triple blind randomized study used to minimize bias and to allow sufficient comparison between groups. The outcome of this study showed that Prednisolone resulted in statistically significant reduction in post endodontic pain at 6, 12 hours post operatively which was considered as large and moderate effect size respectively. At 24 hours postoperatively; Prednisolone group didn’t seem to differ significantly from placebo group with small effect size and this is may be due to prednisolone half-life is from 3 hours to 4 hours. So, in absence of contraindications for corticosteroid administration, the use of single-dose prednisolone appears to be a safe and effective method to reduce postoperative pain. It is possible that these favorable results might help to prevent post-endodontic pain.