Purpose:-The purpose of this randomized clinical trial was to compare the efficacy of 20% and 50% concentration of magnesium sulfate and ketorolac in increasing the effectiveness of inferior alveolar nerve block in patients with symptoms of irreversible pulpitis. Materials and method :- Fifty-six subjects with symptoms of irreversible pulpitis in mandibular molars were included in the study. Heft-parker visual analog scale (HP-VAS) was used to evaluate the initial pain and pain during access cavity preparation. Fifty six patients were randomly divided into 4 groups (n=14). 1 hour before administration of conventional IAN block one group received 1 ml magnesium sulfate USP 20% and the other groups received 50% magnesium sulfate, ketorolac and distilled water (placebo) respectively. After IANB injection when the patient reported of lip numbness and showed two negative responses to the electric pulp tester endodontic access cavity preparation was started. The patient’s pain during access cavity preparation and initial instrumentation is evaluated by using HP-VAS. Result:- There was no statistical difference for the effect of gender, age and initial pain between the four groups. Anesthetic success for IAN block was more for ketorolac followed by 50% magnesium sulfate and 20% magnesium sulfate. Conclusion:- Ketorolac is more effective in increasing the efficacy of inferior alveolar nerve block followed by 50% magnesium sulfate and 20% magnesium sulfate.