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 concentration and application time of NaOCl can decrease the decalcification effect of chelating agents.