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This ex vivo study aimed to evaluate the efficacy of retreating GuttaCore (Dentsply Tulsa Dental Specialties, Tulsa, OK) and warm vertically condensed gutta-percha in moderately curved canals with 2 different systems: ProTaper Universal Retreatment (Dentsply Tulsa Dental) and WaveOne (Dentsply Tulsa Dental).Eighty mesial roots of mandibular molars were used in this study. The mesiobuccal canals in each sample were prepared to length with the WaveOne Primary file (Dentsply Tulsa Dental). The canals were obturated with either a warm vertical approach or with GuttaCore and divided into 4 retreatment groups with the same mean root curvature: warm vertical retreated with ProTaper, warm vertical retreated with WaveOne, GuttaCore retreated with ProTaper, and GuttaCore retreated with WaveOne. The warm vertical groups were obturated using a continuous-wave technique of gutta-percha compaction, and the GuttaCore groups were obturated according to the manufacturer's instructions. After allowing sealer to set, each specimen was retreated with either the ProTaper Universal Retreatment files D1, D2, or D3 or with the WaveOne Primary file to the predetermined working length. The time taken to reach the working length was recorded. Instrument fatigue and failure were also evaluated.The post hoc 2-sample t tests showed that the overall mean total time taken to reach the working length for the warm vertical groups was significantly greater than that observed for the GuttaCore groups (mean = 87.11 vs 60.16 seconds, respectively), and the overall mean total time taken to reach the working length for WaveOne was significantly greater than that observed for ProTaper (99.09 vs 48.18 seconds, respectively). Two-way analysis of variance showed a significant main effect for both the type of experiment groups (F1,76 = 15.32, P = .0002) and the type of retreatments (F1,76 = 54.67, P < .0001). Also, the WaveOne Primary file underwent more separations than the ProTaper files.The WaveOne Primary file underwent more separations and was unable to remove gutta-percha as efficiently as the ProTaper Universal Retreatment files. Also, canals obturated with GuttaCore were retreated more efficiently and with fewer file separations than the canals obturated using continuous wave of warm gutta-percha.WaveOne Primary was unable to remove gutta-percha as efficiently.WaveOne Primary underwent more file separations and unwindings.Canals obturated with GuttaCore were able to be retreated more efficiently.Canals obturated with GuttaCore were able to be retreated with fewer file separations and unwindings.