The aim of this study was to evaluate the effect of mental-incisive nerve block (MINB) along with finger pressure following inferior alveolar nerve block (IANB) on anesthetic success in mandibular first molars with asymptomatic irreversible pulpitis. In this randomized controlled trial, 70 patients were randomly divided into 2 groups (n = 35). Each patient in the control group received only a standard IANB injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The injection was administered within 1 minute, using a standard aspirating dental cartridge fitted with a 27-gauge dental needle. In the intervention group, 15 minutes after injection of the standard IANB as described for the control group, each patient received a standard MINB injection of 1 mL of 2% lidocaine containing 1:100,000 epinephrine, administered by an operator not involved in assessing the outcomes. After the MINB injection, the patient applied firm finger pressure to the soft tissue of the mental foramen region for 1 minute using the hand on the side opposite to the injection. Objective assessment of tooth anesthesia was carried out with electric pulp tests (EPTs). In addition, the patients rated their pain during the initial steps of endodontic treatment based on a visual analog scale (VAS). The Mann-Whitney U and Wilcoxon tests were used for the analysis of data. Of the 35 patients in each group, 20.0% (7 patients) in the control group and 71.4% (25 patients) in the intervention group had no response to EPTs 15 minutes after injections; this difference was statistically significant (P < 0.05). The VAS pain scores were significantly higher in the control group than in the intervention group (P = 0.001). The administration of MINB with pressure following IANB significantly improved the success of anesthesia in mandibular first molars with asymptomatic irreversible pulpitis.