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Introduction: WaveOne is a single-file reciprocating instrumentation system with the benefits of M-Wire alloy that has increased flexibility and improved resistance to cyclic fatigue over the conventional alloy. Root canal preparation techniques may cause postoperative pain. The goal of the present study was to compare the intensity and duration of postoperative pain when using WaveOne or ProTaper Universal systems for instrumentation of root canals., Methods: Forty-two patients who fulfilled specific inclusion criteria were assigned to 2 groups according to the root canal instrumentation technique used, WaveOne or ProTaper Universal. Root canal treatment was carried out in 2 appointments, and the severity of postoperative pain was assessed by numerical rating scale (NRS) score after each session until complete pain relief was achieved. Analgesic consumption, duration of pain, and root canal preparation time were also recorded., Results: The mean NRS score and duration of pain after both appointments were significantly higher in the WaveOne group (P < .05); however, the mean analgesic consumption was only significantly higher in the WaveOne group after the first appointment (P < .05). In all groups the highest mean NRS score was seen 6 hours after each therapeutic appointment. Canal preparation time was significantly shorter in the WaveOne group (P < .001)., Conclusions: Postoperative pain was significantly lower in patients undergoing canal instrumentation with ProTaper Universal rotary instruments compared with the WaveOne reciprocating single-file technique., (Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)