This randomized clinical trial was conducted to evaluate and compare the post-operative pain after using two different irrigation tips: end-vented NaviTip tip and side-vented NaviTip tip in single-visit root canal treatment immediately post-operative and 4, 12, 24 ,48, 72-hrs and 7 days after treatment using a NRS.Thirty-eight patients with vital, lower posterior teeth without periapical radiolucency were randomized into two equal group according to the needle used for irrigation; Group E: end-vented NaviTip or Group S: side-vented NaviTip. All teeth were treated using the ProTaper system and obturated in a single-visit. All demographic data, clinical and radiographic findings and NRS scores obtained from patients were statistically analyzed.There was no statistically significance difference in the baseline factors between groups (p> 0.05). Results showed that there was a statistically significance difference in post-operative pain intensity between the two group at 4 and 12-h post-operatively (p<0.05). There was a statistically significance decrease in post-operative pain after 12-h compared to pre-operative pain for both groups (p<0.05). Both groups, however, did not differ in medication intake (p>0.05). - Within the limitations of this study, it could be concluded that:1.Side-vented NaviTip tips seem to cause less post-operative pain than end-vented NaviTip tips within the first 24 hour and, thus, can be considered safer during the treatment of mandibular, posterior teeth in one visit.2.Pain intensity seemed to decrease by time in both groups after 24-hrs post-operatively, till it disappears.3.Within the limitations of this study, it could be recommended to use side-vented NaviTip irrigator tips to decrease post-operative pain in patients with symptomatic or asymptomatic irreversible pulpitis in mandibular, posterior teeth treated in single-visit.