Introduction: This study compared the efficacy of four anesthetic solutions for inferior alveolar nerve block (IANB) in patients with irreversible pulpitis. Material and Methods: This prospective, randomized, double-blind tudy included 60 adult volunteers. The patients were randomly divided into four groups of 15 and received conventional IANB as follows: Group ART - 2 cartridges of 4% articaine with 1:100,000 epinephrine, Group LID - 2 cartridges of 2% lidocaine with 1:100,000 epinephrine, Group PRI - 2 cartridges of 3% prilocaine with 0.03 IU felypressin; and Group MEP - 2 cartridges of 2% mepivacaine with 1:100,000 epinephrine. Access was begun 10 minutes after IANB, and patients were instructed to rate any pain felt during the endodontic procedure. The success of IANB was defined as access and instrumentation of root canals with no pain. If the patient felt any pain, the treatment was discontinued immediately and the anesthetic procedure was classified as unsuccessful. Results: The chi-square test was used to analyze results (α = 5%). There was no significant difference (p > 0.05) in the efficacy of IANB between the ART (53.33%), PRI (46.66%), and MEP (53.33%) groups. However, the success rate in the LID group was statistically lower (20%) than in the other groups (p < 0.05). Conclusion: None of the anesthetic solutions had an acceptable success rate for IANB in patients with irreversible pulpitis. 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