Factors Associated With Endodontic Flare‐Ups: A Systematic Review and Meta‐Analysis

BACKGROUND: Endodontic flare-ups, characterized by severe postoperative pain and/or swelling requiring unscheduled intervention, remain a clinically significant concern in root canal therapy. Identifying the factors associated with flare-ups is important for anticipating and managing patient outcomes. OBJECTIVES: This systematic review and meta-analysis aimed to identify and synthesize clinical risk factors associated with endodontic flare-ups following root canal treatment. METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus from database inception to September 2025. Eligible studies included observational or interventional studies evaluating the association between potential risk factors and flare-up occurrence. Risk of bias was assessed using ROBINS-I for non-randomized studies and the Cochrane RoB 2 tool for randomized controlled trials. Certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 15 eligible studies involving 24 320 cases met the inclusion criteria. The overall incidence of severe flare-ups was 2.83%. Significant risk factors included female sex, mandibular tooth location, non-vital pulp status, preoperative spontaneous pain, periapical lesions, multiple-visit treatment, re-treatment, and preoperative percussion pain. Among these, preoperative spontaneous pain (relative risk = 5.83) and percussion pain (relative risk = 3.45) demonstrated the strongest associations. By contrast, age, tooth type, number of root canals, instrumentation technique, and preoperative analgesic use were not significantly associated with flare-up incidence. CONCLUSION: Several clinical factors appear to be associated with an increased risk of endodontic flare-ups. Although the overall certainty of evidence is low, these findings may assist clinicians in identifying higher-risk cases and counselling patients regarding potential postoperative outcomes. Further well-designed prospective studies are needed to strengthen the evidence base. TRAIL REGISTRATION: PROSPERO Systematic review registration number: CRD420251025451.