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The intentional enlargement of the apical foramen is designed to reduce the microbial load in the apical foramen, or even beyond, to levels more favorable for repair. This study provides a systematic review and meta-analysis to address the PICOS question: in adult patients who undergo endodontic treatment, does foraminal enlargement (FE) cause different postoperative symptoms in comparison with conventional endodontic treatment?The PROSPERO registration number is CRD42017059921 and was conducted following the PRISMA statements. A broad search was conducted in the electronic databases PubMed, Web of Science, Scopus, Cochrane Library, and grey literature for articles published through May 2017. The MeSH terms “Pain,” “Hyperemia,” “Edema,” “Hyperesthesia,” “Fistula,” “Root canal preparation,” “Tooth apex,” “Periapical periodontitis,” “Dental pulp necrosis,” and “Clinical study” were used. The reviewers evaluated the studies for eligibility criteria and performed data abstraction and risk of bias evaluations. A random-effects model was used for the meta-analysis.Five studies qualified for systematic review, and 3 studies were considered for meta-analysis. The results of the meta-analysis showed that postoperative pain is higher in the endodontic treatment with FE, with a statistically significant difference in the first, second, fourth, sixth, and seventh days. Limited data indicated that no significant difference was found in analgesic consumption, flare-up, and swelling between the groups.Postoperative pain was higher in the FE group compared with conventional endodontic therapy in the first days after treatment in teeth with necrosis and apical periodontitis.The relationship between foraminal enlargement and postoperative pain is unknown.Five studies were included in the systematic review.Meta-analysis showed that foraminal enlargement provides higher pain in the first days.Cautious and rational approach is advised when considering foraminal enlargement.