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The aim of this study was to evaluate the effect of initial NaOCl on the decalcification and erosion ability of EDTA and QMix. Sixty‐maxillary‐incisors were bisected longitudinally and the tooth‐halves were used. The experiment was conducted in two‐sets. In set‐I, 80‐tooth halves were treated in the presence or absence of initial NaOCl and EDTA. In set‐II, 40‐tooth halves were immersed in NaOCl and QMix. After each treatment, calcium‐ion release was determined with flame photometry. The erosion was imaged using SEM. Initial NaOCl led to concentration‐ and time‐dependent increase in calcium removal effect of 17% EDTA (p < .05). The rate of calcium removal and root canal wall erosion was considerably more severe with the use of 5% NaOCl for 3 min (p < .05). QMix as a final solution showed less decalcification and erosion than 17% EDTA when used 5% NaOCl as an initial irrigant (p < .05). Optimizing the …