Pain is the primary reason that dental patients seek endodontic therapy. The inferior alveolar nerve block (IANB) is the most frequently used mandibular injection technique for achieving local anesthesia for endodontic treatment. However, the IANB does not always result in successful pulpal anesthesia. Therefore, the purpose of this study was to determine the effects of preoperative administration of paracetamol and ketorolac on the efficacy of the IANB in patients with irreversible pulpitis. Material and Method: A total of 45 patients diagnosed with irreversible pulpits of a mandibular posterior tooth randomly received identical capsules of either 650 mg paracetamol or 10 mg ketorolac or a placebo 30 min before the administration of a conventional IANB. IANB was administered under aseptic conditions by using 2% lignocaine with 1:100000 adrenaline. After 15 minutes, access cavity preparation was initiated and patients were asked to inform if they experienced pain. Patients were excluded from the study if they experienced pain but if the patient did not feel pain endodontic treatment was continued. p-value was set at 0.05. Data was analyzed by using Chi-square test (SPSS 22). Result: Ketorolac was associated with superior efficacy in pain reduction when compared with paracetamol and placebo. Conclusion: In conclusion, for mandibular posterior teeth, a preoperative dose of 10 mg of ketorolac showed a statistically significant increase in the success of the IANB in patients with irreversible pulpitis.