AimTo evaluate the effect of cold and room-temperature normal saline as a final irrigation on post-endodontic pain and to compare the post-endodontic pain level between the different protocols.Materials and methodsA randomized controlled trial was conducted on 105 patients who underwent RCT and were distributed blindly and randomly into three equal groups (n = 35): Group 1, Cryotherapy group; Group 2, Room- temperature normal saline group; and Group 3, Control group. The patients were asked to fill out the VAS questionnaire and register their post-endodontic pain at 6, 24, and 48 h. One-way analysis of variance (ANOVA) and was used to determine statistical difference (α = 0.05) among the groups. Tuckey’s test was used to calculate P-value (α = 0.05) between two each group.ResultsThe highest post-endodontic pain was in Group 3. There was no significance difference between Group 1 and Group 2.ConclusionFinal flushing of the canal with saline either cold or at room temperature was effective for post-endodontic pain control. This can be promising as an essential step in endodontic treatment to reduce post-endodontic pain. The room-temperature saline as final irrigation showed comparable results to intra-canal cryotherapy.