Background: Extrusion of debris is a major factor that results in postoperative pain during root canal treatment with various instruments and instrumentation techniques. Therefore, instrumentation techniques that extrude minimal debris into the periapical area while reducing pain are desirable. This study aimed to compare the incidence of postoperative pain and intake of analgesic medication (frequency and quantity) after endodontic treatment of mandibular posterior teeth using two single files and full-sequence continuous rotary systems with different kinematic motions. Methods: Thirty-five of 105 patients were assigned equally to three groups according to the instrumentation system used: ProTaper Next (PN) X2, 25/06 (Dentsply, Maillefer, Ballaigues, Switzerland), One Shape (OS), #0.25/06 (Micro Mega, Besancon, France), and Wave One Gold (WG), Red - #0.25, 0.07 (Dentsply, Maillefer, Ballaigues, Switzerland). Five specialists were included in this study design; each professional prepared 21 teeth, and randomly selected 7 per instrument system. The VAS sheet ranging from 0 to 10 was used to record the initial and postoperative pains at 24, 48, and 72 h, and 7th day after single visit endodontic treatment in mandibular premolars and molars with a diagnosis of asymptomatic irreversible pulpitis with or without apical periodontitis. Postoperatively, an analgesic, ibuprofen 400 mg was administered for intolerable pain at a dose of 1 tablet for 6 h. The patients were asked over the telephone regarding postoperative pain at intervals of 24, 48, and 72 h, and 7 th day using a visual analogue scale.Result: There were no statistically significant differences among the PN, OS, and WG systems (P > 0.05) with regard to the incidence of postoperative pain at any of the four time points assessed. Conclusion The intensity of postoperative pain, frequency, and analgesic intake were similar across all three types of instrument systems; however, the reciprocating single file (WG) was associated with less postoperative pain than the full sequence continuous rotary file.