Background: Inferior alveolar nerve block (IANB) is known to have a lower success rate for anesthesia in patients with irreversible pulpitis. This calls for supplementary techniques to effectively anesthetize such patients.This systematic review aimed to evaluate the published literature for determining the success rate of anesthesia induction using post-IANB intraligamentary (IL) injection in the mandibular teeth of patients with symptomatic irreversible pulpitis. The review question was, “What is the success rate of IL injection in the mandibular teeth of patients with irreversible pulpitis as a supplementary technique for endodontic treatment?” Methods: A thorough search of electronic databases and manual searches were performed. The protocol of the review was framed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO) with a proper criterion for inclusion and exclusion of studies. The included studies were analyzed using the Cochrane Collaboration ‘‘Risk of Bias’’ tool. A meta-analysis that included a comparison of primary nerve block and supplemental IL injection was performed. The success rate was evaluated using the combined risk ratio (RR) with a random risk model. A funnel plot was created to measure publication bias. Results: After all analyses, four studies were included. In the forest plot representation, RRs were 3.56 (95% CI: 2.86, 4.44), which were in favor of the supplemental IL injections. Statistical heterogeneity was found to be 0%. These values suggest that supplemental IL injections provide better success rates for anesthesia. Conclusion According to the pooled qualitative and quantitative analyses, supplemental IL injections increased anesthetic efficacy.