This randomized clinical trial aims to evaluate cryotherapy as a therapeutic option for pain prevention after endodontic treatment with and without foraminal enlargement, in patients with asymptomatic apical periodontitis.120 teeth of patients with preoperative Visual Analogue Scale score indicating zero were treated. Specimens were randomly allocated into 4 groups: Control, Cryotherapy (ICT), Foraminal Enlargement (FE), and Cryotherapy and Foraminal Enlargement (ICT + FE). Working length was determined with an Electronic Apex Locator (EAL). Cryotherapy groups passed through a final irrigation protocol using 20 ml (2.5 ℃) of cold saline solution delivered at working length for 5 min. In FE groups a #40 K-file was used up to the 0.0 mark on the EAL display. Obturation was performed and postoperative pain was checked at 6, 12, 24, 48, and 72 h and 7 days after endodontic treatment.All experimental groups showed an increase in the level of postoperative pain, which started to decrease after 12 h. Foraminal enlargement caused a statistically significant increase in postoperativepain compared to ICT and control groups within the first 6 h (p < 0.05). Cryotherapy did not influence postoperative pain, regardless of whether or not foraminal enlargement was performed.