Introduction: The purpose of this study was to compare between 2% mepivacaine and 4% articaine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis in mandibular molars as regards to their anesthetic efficiency, during access cavity preparation and instrumentation utilizing a numerical rating scale (NRS).Methods: Sixty-six patients with irreversible pulpitis admitted to the department of endodontics, faculty of oral and dental medicine, Cairo University, Egypt, randomly received a conventional inferior alveolar nerve block containing either 3.6 ml of 2% mepivacaine hydrochloride with 1:100,000 epinephrine or 3.4 ml of 4% articaine hydrochloride with 1:100,000 epinephrine. During access cavity preparation and instrumentation, the patients were instructed to report any painful sensation and mark his/ her level of pain on the numerical rating scale (NRS). Results: Each group showed statistically significant difference in the incidence of pain degrees (no pains, mild pain, moderate pain, sever pain) at different levels (Pre-operative, during access cavity and during instrumentation). The success rate for the IAN block using the mepivacaine solution was 39% (13of 33) and for the articaine solution success was 45% (15of 33), There was no statistical significant difference between the two solutions. Conclusions: Neither 2% mepivacaine with 1:100,000 epinephrine nor 4% articaine with 1:100,000 epinephrine, administered in a conventional IAN block, were entirely efficient in controlling pain during the treatment of symptomatic irreversible pulpitis.