This systematic review and meta-analysis aimed to determine whether apical patency increases postoperative pain after endodontic therapy. This study explored the degree and incidence of postoperative pain during root canal therapy, as well as the number of required analgesic doses. We searched PubMed, Scopus, Embase, Web of Science, Cochrane Library, and gray literature from the date of database inception until May 2023. RevMan 5.4 software was used for data analysis. Twelve studies were considered eligible for meta-analysis. The mean pain scores on days 1 (mean difference [MD] = -1.69) and 2 (MD = -0.85) differed significantly between the apical patency and non-patency groups. The odds for pain after 24 h were significantly lower (OR 0.59) in the apical patency group than in the non-patency group. Furthermore, the mean number of required analgesic doses was not significantly different between the two groups. In conclusion, apical patency significantly alleviated postoperative pain (low-quality evidence) and reduced the incidence of pain (moderate evidence). However, high-quality randomized controlled trials are required to validate these findings.© 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.