Abstract : Post-endodontic pain can occur due to periapical tissue injury by mechanical, chemical and microbial factors. Many methods including cryotherapy were introduced to reduce post-endodontic pain, therefore this study aimed to evaluate the effectiveness of intracanal cryotherapy on reducing post-endodontic pain. The studied sample consisted of 30 root canal treatment in 15 patients aged between 22-49 years, they were allocated randomly into two groups: Group 1 (n=15, Experimental) root canal treatment in one session and final irrigation with sterile cold (2.5 ° C) saline delivered to 3 mm short of the working length for 5 minutes, and Group 2 (n=15, Control) root canal treatment in one session and final irrigation with sterile room temperature saline delivered to 3 mm short of the working length for 5 minutes. Post-endodontic pain was evaluated using visual analogue scale (VAS) after 6, 12, 24, 48, 72 hours of root canal treatment. Data were analyzed using independent t-test. A statistically significant difference between the cryotherapy and control groups was found after 6, 12, 24, 48 hours of the treatment (p<0.005), while no statistically significant difference was found between the two studied groups after 72 hours of the treatment. Intracanal cryotherapy using sterile cold (2.5 ° C) saline for 5 minutes as a final rinse can significantly reduce the post-endodontic pain.