Abstract
Objectives: To critically evaluate the clinical evidence on patient-, tooth-, biology-, and treatment-related risk factors for endodontic flare-ups and postoperative pain after nonsurgical root canal therapy. Particular emphasis was placed on the issue of inconsistent results due to differences in definitions and methodological issues. Materials and Methods: PubMed and Scopus were searched on 28 June 2026 using specific search strategies within each database that encompassed endodontic therapy, post-treatment pain, risk factors, and pulpal and periapical lesions. The eligible publications consisted of English clinical studies that had been published from 28 June 2006 to 28 June 2026. Title and abstract screening, full-text eligibility assessment, and data extraction were performed by a single reviewer without independent second-reviewer verification. Seventeen eligible reports were included in the revised narrative synthesis, comprising 13 from the original database searches and four identified through supplementary reference screening. Related genetic publications were considered together because of confirmed or suspected overlap in their patient populations. Due to heterogeneity in study populations, outcome definitions, treatment protocols, follow-up periods, and statistical analyses, findings were evaluated through critical appraisal and narrative synthesis. Results: Preoperative pain showed the strongest association with postoperative pain, whereas evidence specifically addressing clinically defined endodontic flare-ups was more limited. Associations for periapical condition, pulpal diagnosis, and the number of appointments were variable among studies. There was insufficient evidence or inconsistency on the role of age, sex, tooth factors, irrigation, instrumentation, and obturation factors. Psychological factors and genetic polymorphisms emerged as potential factors associated with postoperative pain, although their clinical relevance remains uncertain. Differences in outcome definitions, patient populations, treatment protocols, and adjustment for confounding variables may have contributed to discrepancies between studies. Conclusions: Flare-ups and postoperative pain are two different conditions that have some similarities but must be assessed independently of each other. Preoperative pain can be considered one of the main factors related to postoperative pain. However, the relatively small and methodologically heterogeneous evidence base limits firm conclusions regarding individual risk factors, particularly for clinically defined flare-ups. Further outcome-specific investigations are needed. Clinical Relevance: Evaluation of preoperative symptoms and relevant clinical characteristics may support patient counseling and treatment planning. However, there is no valid predictive tool for individual endodontic flare-ups based on the current literature.