Aim: To investigate the effect of magnesium sulphate used as an adjuvant to lidocaine with epinephrine local anaesthetic on the success of inferior alveolar nerve blocks (IANB) in patients with symptoms of irreversible pulpitis undergoing root canal treatment. Methodology: In a double-blind clinical trial, following power calculation, 124 patients with symptoms of irreversible pulpitis in mandibular molar teeth were selected, and initial pain data were collected using a Heft–Parker (Pain, 19, 1984 and 153) visual analogue scale. The first group (control) received IANB with 1.8 mL of a local anaesthetic solution containing 1.8% lidocaine with 1 : 88 000 epinephrine while the second group (test) received IANB with 1.8 mL of an anaesthetic solution containing 1% magnesium sulphate, and 1.8% lidocaine with 1 : 88 000 epinephrine. Pain data were collected after access cavity and penetration of files in the canals using a Heft–Parker visual analogue scale. Two patients were not included in the study as they did not consent, and a further 54 patients were excluded as they did not report lip numbness within 15 min after IANB administration; thus, the data presented in this study are related to 68 patients. The data were analysed using chi-square and t-test (α = 0.05). Results: The success of pulpal anaesthesia with IANB was 82% for the magnesium sulphate group and 53% for the control group. There was a significant difference in the effectiveness of the IANB between the two groups (P < 0.001). There was no significant difference between the magnesium sulphate and control groups regarding gender (P = 0.598) or age (P = 0.208) or initial pain scores (P = 0.431). Conclusions: The addition of 1% magnesium sulphate to 1.8% lidocaine with 1 : 88 000 epinephrine resulted in a positive impact for the success of IANB in patients with a diagnosis of irreversible pulpitis related to mandibular molar teeth undergoing root canal treatment. Thus magnesium sulphate may be used as adjuvant for achieving profound pulpal anaesthesia in challenging cases. However, more studies with larger sample size and different concentration doses must be carried out to establish an appropriate conclusion before its routine clinical use.