The main cause of unsuccess in endodontically treated teeth (ETT) is due to bacterial recontamination. The placement of an intraorifice barrier (IOB) has been proposed for preventing this event in cases that the restoration is in an inadequate condition, enhancing the possibilities for predictable long-term success in endodontic therapy. Objectives. To evaluate through a systematic review and meta-analysis if it would be necessary to place an IOB in ETT. Materials and Methods. The present review is in accordance with the PRISMA 2020 Statement and is registered in the Open Science Framework. Two blinded reviewers carried out a comprehensive search in four databases up to July 10th, 2021: MEDLINE, Scopus, Embase, and Web of Science. Eligible studies were the ones which evaluated the use of an IOB in ETT in reducing microleakage with any material of choice and with any methods employed. Only in vitro studies published in English were included. Results. A total of thirty in vitro studies were included in the qualitative synthesis, and seven of those were included in the quantitative analyses evaluating the following materials: bioceramic cement, glass-ionomer cement (GIC), and resin-based composite (RBC). Most of the included studies placed an IOB at a 3 mm depth. Reduction in microleakage was observed when an IOB was placed, regardless of the material employed (
p
≤
0.01
). Among the materials, GIC and RBC performed similarly (
p
>
0.05
), with the bioceramic subgroup being statistically superior to the GIC subgroup (
p
≤
0.05
). Conclusions. Although well-designed randomized clinical trials are required, the placement of an intraorifice barrier can significantly reduce microleakage in endodontically treated teeth, and the use of bioceramics as IOB seems to be the best available material for this purpose.