The aim of this study was to assess the effectiveness of irrigation activation techniques on postoperative pain (PP) in mandibular premolar teeth with irreversible pulpitis after single-visit endodontic treatment. A total of 160 patients with symptomatic irreversible pulpitis were included in this prospective randomized clinical study. Four different activation methods were used in mandibular premolar teeth. In group 1, teeth were irrigated with side-port endodontic needles (NI) without any agitation; in groups 2 and 3, sonic activation was performed using EDDY and EndoActivator (EA), respectively; and in group 4, passive ultrasonic irrigation (PUI) was used. Patients' analgesic intake-as well as pain intensity during and after treatment-were recorded at 8, 24, 48 h and 7 days. The data relating to age, sex and analgesic intake was evaluated using the Chi-square test and the preoperative pain and PP intensity at different time intervals was evaluated with the Kruskal-Wallis test at a 5% significance level. Highest PP was recorded at 8 h, pain intensity decreased in all groups by the time. Pain in the NI group was found higher than that of EDDY group at 24 h (P < 0.05). EA and PUI had caused mild pain and had similar pain scores at 24 h. (P > 0.05). No statistically difference was found among the groups with regard to analgesic intake (P > 0.05). Although there were slight differences in PP levels between the groups at 24 h, pain levels decreased in all groups after 24 h. Activation of the irrigation solution did not make any difference in terms of PP after 24 h.