Background: For the endodontic treatment to be considered successful and accepted readily by the patient and dentist, it must efficiently relieve pain. Local anesthesia, through inhibition of nociceptive signals, is integral to the management of painful endodontic emergencies. A major focus of attention has been put on the reduction of inflammation prior to local anesthesia to enhance the success of anesthetics. Inflammation has been regarded as one of the important factors that play a role in failed anesthetics as mediators of inflammation have the potential to stimulate nociceptor fibers even at very low thresholds and it has been stated that decreasing the amount of prostaglandins may increase the efficacy of local anesthetics. Aim of the study: To compare the effect Laser and Ibuprofen on the Success of Inferior Alveolar Nerve Block in Irreversible Pulpitis. Materials and methods: The present study was conducted in the Department of Endodontics of the Dental institution. For the study, we selected healthy patients having a first or second mandibular molar tooth with irreversible pulpitis and normal periapical radiographic appearance. A total of 60 patients were selected for the study. All patients were adults over 18 years of age. The participants were randomly divided into three groups of 20 patients each. In Group A patients were given 600 mg ibuprofen one hour preoperatively, in Group B patients were given low level laser therapy at the periapical area of the involved tooth for 5 min, and in Group C no ibuprofen or laser treatment was provided. Results: In the present study, we compared the effect of laser therapy and ibuprofen with IANB. The study was conducted on 60 patients. Patients were grouped into 3 groups, Group A, B and C. 20 patients were randomly grouped into each group. we observed that highest success rate was seen in Group A (85%). Group B showed 65% success rate. Lowest success rate was seen in group C (40%). The results on comparison were observed to be statistically significant. Conclusion: Within the limitations of the present study, it can be concluded that Ibuprofen and laser therapy provides significant synergistic effect with inferior alveolar nerve block. Success rate of Ibuprofen is higher as compared to laser therapy.