Objective The goal of this systematic review and meta-analysis is to determine the performance of 4% Articaine vs. 2% Lidocaine for mandibular and maxillary block and infiltration anaesthesia in patients with irreversible pulpitis (IP). Methods PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, and Open Gray were used to conduct a thorough literature search. A manual search of the reference lists of the publications found was also carried out. Two reviewers critically evaluated the papers for inclusion and exclusion criteria, and data extraction was done on the selected publications. The Cochrane Collaboration Tool and the Minors checklist were used to assess the quality of the selected studies for randomised controlled trials (RCTs) and non-randomised studies, respectively. The RevMan software was used to perform a meta-analysis of the pooled data and subgroups according to the technique of anaesthetic solution delivery, as well as a sensitivity analysis (P Results A total of twenty-six papers were included in the qualitative synthesis, with twenty-two of them being included in the meta-analysis. There were fifteen studies with a low potential for bias, three with a moderate potential for bias, and seven with a high potential for bias. The combined results of the 19 trials in the tooth level unit revealed that 4% articaine had a success rate 1.37 times greater than 2% lidocaine for mandibular teeth (RR, 1.37; 95% CI [1.17-1.62]; P=0.0002). For the maxillary buccal infiltration method, the combined results from the three trials revealed that 4% articaine resulted in a success rate 1.06 times greater than 2% lidocaine (RR, 1.06; 95% CI [0.95-1.2]; P=0.3). Excluding subgroups with a single study in sensitivity analysis for mandibular teeth revealed a substantial improvement in the success rate of the articaine group in treating IP when compared to the lidocaine group. Conclusion The findings of this meta-analysis back up the claim that articaine is more effective than lidocaine in providing anaesthesia in patients with IP. PROSPERO Registration No.: CRD42020204606 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020204606).