Regenerative endodontic treatment (RET) is an alternative treatment for immature teeth, however, its efficacy on mature teeth is still controversial. This review was aimed to assess the level of evidence of clinical and radiographical outcomes of RET in mature teeth and run a meta-analysis to compare its success rate to conventional root canal treatment (CRCT). The electronic databases PubMed, Science Direct and Web of Science were used to search based on inclusion and exclusion criteria. The Randomized controlled clinical trials (RCTs), case series, and case reports studies of the RET in mature teeth published in the English language from January 2010 till December 2021 were selected. A meta-analysis was performed using the random-effects model on the randomized clinical trials that compare the success rate based on clinical and radiographic outcomes of RET and CRCT. From sixteen articles included in the narrative analysis, two studies were subjected to meta-analysis. Different protocol aspects of RET including disinfection, size of apical preparation, intracanal medications, types of scaffolds, barriers and follow-up periods were described. The meta5analysis showed no significant differences in success rate between CRCT (89.47%) and RET (95.45%) at 12 months (P> 0.05), while it showed a significant increase in a positive response to the electrical pulp test of RET (P= 0.010). With the limitations, the adopted protocols of RET are comparable to CRCT and could be a potential approach to treat mature teeth with pulp necrosis and/or apical periodontitis. However, providing more evidence is essential to ascertain these findings
