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The present randomized clinical trial compared the prevalence and intensity of postoperative pain in cases of endodontic reintervention using manual or engine-driven reciprocating instruments. As secondary objectives, the analgesic intake and time required for the root canal filling removal and re-instrumentation were also evaluated. Forty-eight individuals with an endodontically treated single-rooted tooth diagnosed with asymptomatic apical periodontitis were included in the study. Patients were randomly assigned to two comparison groups (n=24/group): reintervention with stainless steel manual instruments or a nickel-titanium reciprocating system (Reciproc; VDW, Munich, Germany). The endodontic reintervention was performed in two sessions with a calcium hydroxide-based intracanal medication applied for 14 days before root canal obturation. Working time for the root canal filling removal and re-instrumentation was recorded with a digital stopwatch. After each visit, postoperative pain intensity was assessed at 12, 24, and 48 hours and seven days using the Numerical Rating Scale (NRS). The patients were also asked about analgesic intake. Data were analyzed using Pearson chi-square, T and Mann-Whitney U tests (α=0.05). No significant differences between groups were found regarding the prevalence and intensity of pain or the need for analgesic intake at any time point (P > 0.05). Working time was significantly shorter in the reciprocating group (18 versus 41 minutes). In conclusion, manual and reciprocating instruments achieved the same results in terms of prevalence and intensity of postoperative pain and analgesic intake. However, filling material removal and re-instrumentation of the root canals were more than twice as fast when using the reciprocating system.