Objectives: The aim of this prospective randomized clinical trial was to compare the degree of post-operative pain and analgesic intake at 0, 4, 12, 24, 48, 72-hrs and 7 days after the use of two different irrigation needles. Subjects and Methods: Thirty eight participants diagnosed with symptomatic or asymptomatic irreversible pulpitis in mandibular posterior teeth received single-visit root canal treatment and were divided randomly into two groups according to the type of needle used during irrigation eitherNaviTip 29-gauge, 27 mm with End-Vented needle (EVN) or NaviTip 31-gauge, 27 mm with Double Sideport Irrigator Tip (SVN). Post-operative pain was measured using Numeric Rating Scale (NRS) pre-operatively, immediate post-operatively and at 4, 12, 24, 48, 72-hrs and 7 days. Placebo and analgesic intake was recorded at the different time intervals. Results: The End-Vented NaviTip showed more pain than the Side-Vented NaviTip at 4, 12, 24-hrs. Pain intensity seems to decrease by time in both groups till it disappeared after one week dayswith no difference in drug intake post-operatively between both groups.