Objectives: The effects of different EndoActivator (R) (EA) sonic activation protocols on root canal debridement efficacy were examined. Methods: Rootcanalsin48single-rooted teeth were instrumented, irrigated initially with NaOCl and divided into 6 groups (N = 8) based on the application time of QMix (antimicrobial calcium-chelating irrigant), and the time and sequence of EA irrigant activation Positive Control: 90 s QMix; Negative Control: 90s saline; Group 1A: 15s QMix +15 s QMix with EA-activation; Group 1B: 30s QMix + 30s of QMix with EA-activation; Group 2A: 15s QMix with EA-activation + 15 s QMix; Group 2B: 30s QMix with EA-activation +30 s QMix. Split roots were examined with scanning electron microscopy for assignment of smear and debris scores in locations along the coronal, middle and apical thirds of the canals. The overall cleanliness of pooled canal locations in the Positive Control and the 4 experimental groups were compared with chi-square tests. Results: Significant differences were detected among the 5 groups (P < 0.001). Post hoc pairwise comparisons indicated that the overall canal cleanliness was in the order (from best to worst): 1B = 2B > 2A> 1A> Positive Control. Completely clean canals could not be achieved due to the absence of continuous irrigant flow for EA to clear intraradicular debris. Conclusions: Irrespective of the sonic activation sequence, irrigant activation for 30 s during a 60-s period of QMix application appears to maximise the smear layer and debris removal potential of the EndoActivatore system. Clinical significance: Sonic activation of root canal irrigants produces cleaner root canals and reduces the time required for final delivery of a canal wall smear later-removing irrigant when compared to the use of needle irrigation alone. Published by Elsevier B.V.