PubMed, Scopus, Embase, Web of Science, Cochrane Library, and gray literature up to May 2023. Twelve studies were included for meta-analysis. Two authors screened databases to identify suitable studies, with a third investigator resolving disagreements. Inclusion criteria were randomized controlled trials (RCTs) involving individuals without systemic diseases, who underwent root canal treatment in a permanent tooth with or without apical patency. Outcomes included pain, number of patients with pain and analgesic use. Exclusion criteria included patients who had undergone tooth extraction, incomplete data reports and studies which were not RCTs. There were no limits on publication language. A search of PubMed, Scopus, Embase, Web of Science, Cochrane Library, and gray literature from Google Scholar, ProQuest, OpenAire, and BASE identified 92 articles until May 2023. After removing 42 duplicates, 50 article full texts were assessed. Ultimately, 12 studies were included, seven of which were new relative to previous systematic reviews. Data were analysed using RevMan 5.4 software. Dichotomous categorical data were analysed through the Cochran-Mantel-Haenszel test, with the inverse variance method used for continuous data. Following assessment of heterogeneity with the χ2 test, fixed- or random- effects modeling was used. Pain scores were reported within one week by ten studies, but three were excluded from meta-analysis due to methodological issues. Studies involving participants aged 14-65 years, with pulp necrosis, apical periodontitis, or pulpitis, were included for analysis. Irrigation solutions varied from saline to sodium hypochlorite (2.25-5.25%), EDTA, citric acid, or chlorhexidine. Types of teeth treated included molars and anterior teeth. All studies used a 10# K-file for apical patency and various hand and nickel-titanium instruments for canal preparation. Generally, there was slightly reduced post-operative pain reported through the maintenance of patency. This was evident in the initial post-operative period of 24 h (OR = 1.69, P = 0.002), 1-day (MD = -1.69, P = 0.03) and 2-days (MD = -0.85, P = 0.04), but became non-significant over the remainder of the 7-day monitoring period. There was no significant difference in analgesic use between groups (OR = 0.82, P = 0.42). Studies were classified into three groups based on quality: four high quality with low risk of bias; three moderate quality with some concerns; and five low quality with high risk of bias. Evidence quality varied; pain scores on days 1 and 2 were of low quality, with very low quality for 12 h and days 3-6. High heterogeneity and imprecision were noted, especially in pain measurements and analgesic use. The meta-analysis indicates that during the initial post-operative period, apical patency significantly reduces postoperative pain. However, the findings should be interpreted cautiously due to high heterogeneity and variable evidence quality. Given that apical patency is seen as desirable for achieving the biological aims of endodontic treatment, the fact that it also appears to reduce post-operative pain helps to align patient reported outcome measures with traditional measures indicating success.