Backgrounds: Cryotherapy might help in reducing pain after root canal treatment. This study aimed to investigate the effect of different methods of cryotherapy on post-endodontic pain of one-visit root canal treatment in mandibular molar teeth with symptomatic irreversible pulpitis.Materials and Methods: This clinical trial study enrolled 60 patients with symptomatic irreversible pulpitis in a mandibular molar tooth. Before obturating the root canals, teeth were divided into four groups. Group 1: Control (without cryotherapy) Group 2: intracanal cryotherapy with final canal irrigation with 2.5 °C normal saline for 5 minutes, group 3: intraoral cryotherapy with the application of an ice pack 30 minutes inside the mouth and Group 4: extraoral cryotherapy. Patients’ post-endodontic pain was recorded on the first and third days. Data were analyzed by two-way analysis of variance, Tukey, and LSD post hoc test at the error level of 5%.Results: Pain reduction was highest, respectively, in the intracanal, control, and extraoral cryotherapy groups on the first and third days, although not significant (p>0.05). In each group, pain was reduced on the third day after treatment (P<0.05). Pain showed no relation to gender (p>0.05).Conclusion: Despite the limitations, based on the results of this study, the application of cryotherapy has a limited effect in reducing pain after root canal treatment. Time is more effective than cryotherapy in reducing pain. تفاصيل المقالة