This double blind randomized clinical trial was done to assess and compare the efficacy of 2% Mepivacaine versus 4% Articaine for inferior alveolar nerve block (IANB) in Patients with Symptomatic Irreversible Pulpitis in mandibular molars. Subjects and methods: 66 participants aged between 18-50 years were included in the study. Only vital mandibular molars with symptomatic irreversible pulpitis were selected and treated in one visit. The participants were randomly assigned into two equal groups according to the anesthetic solution used: Articaine group: IANB injection of 3.4 ml Articaine hydrochloride 4% with 1:100 000 epinephrine, Mepivacaine group: IANB injection of 3.6 ml mepivacaine hydrochloride 2% with 1:100000 epinephrine. The access cavity preparation and root canal instrumentation were done 15 minutes after IANB injection. The participants ranked their preoperative pain, pain during access cavity preparation and pain during instrumentation on numerical rating scale (NRS). The number of patients who needed supplemental anesthesia (intra-pulpal) was recorded. Obturation was performed using modified single cone technique. Results: There was no statistically significant difference between the two groups in the efficacy of anesthesia, pain intensity and incidence at the different pain categories during access cavity preparation and root canal instrumentation (P>0.5). There was no significant statistical difference in supplemental anesthesia needed in the two groups (P>0.5). Conclusion: Based on these findings, it could be hypothesized that the efficacy of anesthesia is similar in both Articaine and Mepivacaine groups in mandibular molars with acute pulpitis. Both groups failed to achieve complete pulpal anesthesia in mandibular molars with acute pulpitis with IANB only and they were similar regarding the need for supplemental anesthesia.