Introduction: The purpose of the study was to evaluate the effects of intracanal, intraoral, and extraoral cryotherapy on postoperative pain in molar teeth with symptomatic apical periodontitis. Methods: A total of 100 patients were randomly distributed into 4 groups: control (without cryotherapy application), intracanal cryotherapy application, intraoral cryotherapy application, and extraoral cryotherapy application. The postoperative pain of the patients was recorded at the first, third, fifth, and seventh days. The data were statistically analyzed by using linear regression, chi(2), one-way analysis of variance, Tukey post hoc, and Kruskal-Wallis H tests (P = .05). Results: There were no statistically significant differences among the groups in terms of demographic data (P > .05). The preoperative pain levels and preoperative visual analogue scale (VAS) scores of pain on percussion were similar among the groups (P > .05). The linear regression analysis demonstrated that group variable had the most significant effect on postoperative pain at day 1 (P < .001) among the other variables (group, age, gender, tooth number, preoperative pain levels, and VAS scores of pain on percussion). When compared with the control group, all the cryotherapy groups exhibited less percussion pain and less postoperative pain at the first, third; fifth, and seventh days (P < .05). Conclusions: Within the study limitations, all the cryotherapy applications (intracanal, intraoral, and extraoral) resulted in lower postoperative pain levels and lower VAS scores of pain on percussion versus those of the control group.