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The purpose of this prospective study was to determine the anesthetic efficacy of the supplemental buccal infiltration injection of a cartridge of 4% articaine with 1:100,000 epinephrine in mandibular posterior teeth diagnosed with irreversible pulpitis when the conventional inferior alveolar nerve (IAN) block failed. Fifty-five emergency patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth, received an IAN block and had moderate to severe pain on endodontic access. An infiltration of a cartridge of 4% articaine with 1:100,000 epinephrine was administered buccal to the tooth requiring endodontic treatment. Success of the infiltration injection was defined as no pain or mild pain on endodontic access or instrumentation. The results showed that anesthetic success was obtained in 58% of the mandibular posterior teeth. We can conclude that when the IAN block fails to provide profound pulpal anesthesia, the supplemental buccal infiltration injection of a cartridge of 4% articaine with 1:100,000 epinephrine would be successful 58% of the time for mandibular posterior teeth in patients presenting with irreversible pulpitis. Unfortunately, the modest success rate would not provide predictable pulpal anesthesia for all patients requiring profound anesthesia.