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Apical extrusion of infected debris to the periradicular tissues is considered one of the possible factors related to the occurrence of postoperative pain and inflammation. The goal of the present study is to evaluate and compare the incidence and intensity of postoperative pain using two different nickel-titanium instrumentation techniques: a rotary crown-down technique using TF instruments (SybronEndo, Orange, Ca, USA) and a reciprocating single-file technique using Reciproc instruments (VDW, Munich, Germany). Sixty patients requiring endodontic treatment on permanent premolar and molar teeth with non-vital pulps preoperatively were included in the study. The patients were divided into two groups of 30 patients each, trying to make the groups very similar, concerning the number of root canals, presence of initial pain and periapical lesions. The teeth in group 1 (n = 30) were treated with a crown-down technique using TF instruments whilst those in group 2 (n = 30) were treated with, a single-file technique using Reciproc 08 25. All canals were shaped, cleaned and obturated in a single-visit. The assessment of postoperative pain was carried out at 3 days by using a visual analogue scale. CAi-square tests and independent-sample t-tests to compare the incidence and intensity of postoperative pain of two groups were carried out. A statistically significant difference was found between the two techniques. When comparing patients who developed no pain, the TF instrumentation technique showed significantly better results (chi-square = 4.059 P= 0.039). When evaluating patients experiencing severe pain the incidence of symptoms was significantly higher with the Reciproc technique (chi-square = 7.246 P= 0.023). Since the incidence of preoperative pain, the type of tooth and the pulp and periodontal pathology were quite similar between the two tested groups, and all the other variables (operator, irrigation, and obturation) were identical, the difference in postoperative pain can be mainly related to the different instrumentation technique