Aims: This clinical study aimed to evaluate the effect of different clinical practices with endodontic emergency treatment on postoperative pain in mandibular permanent molar teeth with symptomatic apical periodontitis. Methods: In the present study, root canal treatment was applied to 100 patients who met the inclusion criteria. Patients were randomly assigned to 5 groups (control, nonsteroidal anti-inflammatory drug [NSAID], NSAID and antihistaminic drug combination, placebo drug, and intracanal cryotherapy) using a web program. In the first visit, after preparation with the WaveOne Gold file system, calcium hydroxide (Ca(OH)2) medicament was placed on the root canals. However, after the treatment of the patients was completed, six patients patients were excluded from the study because they did not come to the control appointment 7 days later. After the removal of Ca(OH)2 medicament in the second session, the root canals were obturated according to cold lateral condensation technique and final restorations of the teeth were performed. Patients' preoperative and postoperative pain values (4-8-12-24-48 and 72 hours) determined by visual analog scale (VAS) were recorded. The data were analyzed statistically using analysis of variance, Kruskal-Wallis test, Friedman test, Wilcoxon test, and Chi-square test. Results: According to the results of our study; there was no significant difference between the groups in terms of age, gender, preoperative pain, and postoperative analgesic requirement (P > 0.05). In all groups, there were significant differences between the values of different times (P < 0.05). While initial pain values were higher than the hours after treatment (P < 0.05), there was no significant difference between postoperative pain values (P > 0.05). When the groups in terms of pain scales measured at different times compared with each other; in all times there was no significant difference between the groups (P > 0.05). Conclusion: It was observed that all clinical practices significantly reduced preoperative pain.