Objective: To evaluate the incidence and severity of postoperative pain and analgesics intake after root canal treatment of molars using single file systems: WaveOne (WO; Dentsply Maillefer, Ballaigues, Switzerland) and One Shape (OS; Micro Méga, Besançon, France) versus the Self Adjusting File (SAF; ReDentNova, Ra'anana, Israel). Methods: One hundred and forty-one patients with vital molars indicating for conventional singlevisit root canal treatment were randomly assigned to one of three groups (n = 47) according to the instrumentation system used: WaveOne, One Shape and SAF. Participants were asked to rate the intensity of postoperative pain on a Functional Pain Scale and to record the quantity of prescribed analgesic medication taken after 24 h, 48 h, 72 h and 7 days. Data were statistically analysed using SPSS software (version 20; Chicago, Illinois, USA). Intergroup analysis was performed using the Kruskal-Wallis, followed by Mann-Whitney U tests for intragroup comparison. The Friedman test was applied for comparison between different time intervals. The level of significance was set at P 0.05. Results: Patients treated with the SAF system were associated with significantly less postoperative pain and lower analgesic intake compared to the other two groups at the four timepoints assessed. Conclusion: The SAF system caused less postoperative pain and lower intake of analgesic medication at the timepoints assessed. Keywords: Nickel-Titanium instruments, One Shape, Self Adjusting File, WaveOne