Aim This randomized clinical trial aimed to assess the effect of two rotary (ProTaper Retreatment + ProTaper Gold and Hyflex EDM) and two reciprocating (Reciproc Blue and WaveOne Gold) NiTi systems on postoperative pain after root canal retreatment on single-rooted incisor teeth. Methodology One hundred and eighty patients scheduled for root canal retreatment were randomly assigned to one of the four groups according to the NiTi system (ProTaper Retreatment + ProTaper Gold, Hyflex EDM, Reciproc Blue or WaveOne Gold) used for the removal of root canal fillings and further canal preparation. The working length was determined to be 1 mm shorter than the '0.0' mark of the apex locator. Root canals were filled with gutta-percha and an epoxy resin-based root canal sealer using a lateral compaction technique. The teeth were restored using a resin composite material. A single operator performed the retreatments in a single visit. The incidence and intensity of postoperative pain were rated on a numeric rating scale by patients 24, 48 and 72 h after retreatment. The number of analgesic tablets (400 mg Ibuprofen) taken by patients was also recorded. Data were analysed using the Mann-Whitney U, Wilcoxon and chi-square tests. Results For the intensity of postoperative pain, the difference between the four groups was not significantly different (p > .05). No significant difference was found between the groups in terms of analgesic medication intake (p > .05). Conclusions The rotary and reciprocating NiTi systems tested in this study were associated with similar intensity of postoperative pain and intake of analgesics following root canal retreatment on single-rooted incisor teeth completed in one visit.