This systematic review and network meta-analysis aimed to answer the following focused research question: “Does the type of endodontic sealer affect the postoperative pain in patients who received endodontic treatment?” Different databases and grey literature were surveyed. Only one randomized controlled trial were included. The risk of bias in the studies was evaluated by using the Cochrane Collaboration’s tool. A random-effects metaanalysis was conducted to compare the risk and intensity of postoperative pain. The quality of the body of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Out of 11,601 studies, 15 remained for qualitative analyses and 12 for meta-analysis. Seven studies were classified at high risk of bias, and 8 studies raised some concerns. No significant differences between the endodontic materials were observed in the direct comparisons, both in risk and in intensity of postoperative pain (pairwise comparisons with 2 studies: I2 = 0%; p > 0.05 and 8 studies: I2 = 23%; p > 0.05, respectively). The certainty of the evidence was graded as low or moderate. There was no difference in the risk and intensity of postoperative pain after filling with different endodontic sealers. Further systematic reviews should be conducted.