Introduction: Root canal therapy of teeth can stop the endodontic pain, but the cousequent post-endodontic pain and discomfort are undesirable effects. There are many studies on various drugs for alleviation of post-endodontic pain. The purpose of this study was to compare the Efficacy of prophylactic use of Teltonal in comparison with Ibuprofen on post- endodontic pain.Materials & Methods: In this triple-blind clinical trial study, 57 patients with anterior vital single rooted teeth and severe decay were selected. Patients were divided into three groups of A, B and C. One capsule was given to each patient as prophylaxis before the treatment, which according to its code contained Ibuprofen, Teltonal or Placebo. Intensity of pain was recorded by the patients before treatment and 6, 12, 24, 48 and 72 hours after the treatment using a VAS scale. The collected data were processed in SPSS-21, and to compare pain during the evaluation periods in all three groups studied, two-way repeated measure ANOVA was used.Results: In each of the three study groups during the evaluation period, the average pain was significantly reduced (P<0.001). However, the difference between the gtoupd was not statistically significant (P=0.347).Conclusion: Since no statistically significant difference was observed between the groups, prophylactic use of these drugs for reduction of post-endodontic pain is not suggested.