BackgroundThis clinical study aims to compare postoperative pain after single-visit root canal treatment of teeth with asymptomatic apical periodontitis using epoxy-resin-based AH Plus and calcium silicate-based Endosequence BC sealers with or without sonic activation.MethodsThis study included 72 individuals with one first or second mandibular premolar tooth with asymptomatic apical periodontitis. They were randomly divided into four groups according to the root canal sealer (AH Plus or Endosequence BC) and activation protocol (sonic activation or non-activation) (n = 18). The participants were ask to rate their postoperative pain intensity on a NRS scale as none, minimal, moderate, or severe after 24 h, 48 h, 72 h, and 7 days following treatment. Patients were also asked to record the number of prescribed analgesic medication tablets (400 mg of ibuprofen) taken. Statistical analysis were performed using the Mann-Whitney U test, the Friedman test, the Spearman’s correlation test, the Chi-square test. Significance level was established at 0.05.ResultsThere was no statistically significant difference in postoperative pain scores or analgesic intake between AH Plus and Endosequence BC sealers regardless of the activation protocol (p > 0.05). There was no statistically significant difference in postoperative pain scores between the sonic activation and non-activation groups (p > 0.05). A weak positive correlation was detected between Endoactivator sonic activation and sealer extrusion (r = 0.36).ConclusionsAH Plus and EndoSequence BC root canal sealers showed similar results in terms of prevalance and intensity of postoperative pain. Sonic activation and non-activation groups had similar postoperative pain scores.Clinical trial registrationThe study was retrospectively registered with ClinicalTrials.gov (NCT06403293). Date of Registration: 07/05/24.