Objective This study aimed to assess the effect of sodium hypochlorite (NaOCl) combined with a novel chelating agent DualRinse HEDP (Medcem GmbH, Weinfelden, Switzerland), a product consisting of 0.9 g of 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) powder, with or without high-power sonic activation on debris and smear layer removal. Methods Seventy-five mandibular premolars were divided into 5 groups (n=15) and treated with different irrigation protocols: group 1 (D3N), DualRinse HEDP+3% NaOCl without activation; group 2 (D3NA), DualRinse HEDP+3% NaOCl with activation (EDDY, VDW, Munich, Germany) during the final irrigation; group 3 (3NE), 3% NaOCl+17% Ethylenediaminetetracetic acid (EDTA)+3% NaOCl without activation; group 4 (3NEA), 3% NaOCl+17% EDTA+3% NaOCl with activation during the final irrigation; group 5 (NC), negative control group, 0.9% saline. Samples were analysed by scanning electron microscopy (SEM) to evaluate residual debris and smear layer at 3 levels of the root canal: coronal, middle, and apical. Statistical analysis was performed with a level of significance set at p<0.05. The normality distribution of scores within each group was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. A Kruskal-Wallis test followed by multiple comparison tests was used to compare scores among the 5 groups on the apical, middle, and coronal levels of the root canal. A Friedman test followed by multiple comparison tests was used to compare scores within the apical, middle, and coronal levels for each treatment group. Results Debris score was significantly the lowest for D3NA, followed by D3N, 3NEA and 3NE at all root levels (p<0.05). The smear layer score was significantly the lowest for D3NA, followed by D3N, 3NEA and 3NE only at the apical level, while no significant difference was found in the middle and coronal levels between the groups (p<0.05). DualRinse HEDP resulted in less debris and smear layer compared to the classic approach of NaOCl without activation. Implementing sonic activation further improved debris and smear layer removal. Conclusion DualRinse HEDP+3% NaOCl improved debris removal at all levels and smear layer elimination at the apical level of the root canal. These results were further enhanced when adding high-power sonic activation.