SummaryAims. Apical extrusion of infected debris to the periradicular tissues is one of the principal causes of postoperative pain and discomfort. Recent researches have shown that reciprocating instrumentation techniques seem to significantly increase the amount of debris extruded beyond the apex and, consequently, the risk of postoperative pain. The goal of the present study was to evaluate and compare postoperative pain using three different nickel-titanium instrumentation techniques: a rotary crown-down technique using TF instruments (SybronEndo, Orange, Ca), a reciprocating single-file technique using WaveOne instruments (Maillefer DEntsply, Baillagues, CH), and a novel instrumentation technique (TF Adaptive, SybronEndo, Orange, Ca), using a unique, proprietary movement, combining reciprocation and continuous rotation. Methods. Ninety patients requiring endodontic treatment on permanent premolar and molar teeth with non vital pulps preoperatively were included in the study. The patients were assigned into three 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 instrumented with a crown-down technique using TF instruments, whilst those in group 2 (n = 30) were instrumented with a single-file technique using Waveone 08 25. The third group (n = 30) used the 3-file Tf Adaprtive sequence. All techniques were performed following manufacturers' instructions and all canals were shaped, cleaned and obturated in a single-visit by the same operator. The assessment of postoperative pain was carried out at 3 days by using a visual analogue scale. VAS pain scores were compared using one-way ANOVA post hoc Tukey test. A value of p < 0.05 was required for statistical significance. Results. Results for VAS pain scores showed a statistically significant difference was found between the WaveOne (p=0,021) technique and the other two techniques. No statistical significant differences were found between TF and TF Adaptive (p= 0,087). When evaluating patient experiencing sever pain the incidence of symptoms was significantly higher with the WaveOne technique. Conclusions. Since the incidence of preoperative pain, the type of tooth and the pulp and periodontal pathology were quite similar between the three tested groups, and all the other variables (operator, irrigation, obturation) were identical, we may conclude that the difference in postoperative pain can be mainly related to the different instrumentation techniques.