Statement of the Problem: Root canal therapy should not simply be the extirpation of the pulp and widening of the canal. But one should also focus on how to completely remove the loosely-attached smear layer because it has adverse effects on the final outcome of the treatment.Purpose: This study compared the efficacy of Etidronic acid, SmearClear and MTAD to remove the smear layer created during instrumentation in different regions of the root canal.Materials and Method: Fifty single-rooted mandibular premolars were decoronated from the cementoenamel junction and instrumented using the ProTaper universal rotary file system along with copious irrigation by 1.0% sodium hypochlorite and distilled water. On the basis of the type of chelating agent used for irrigation, samples (n=10) were then randomized into five groups as: Group I- 9% etidronic acid, Group II- 18% etidronic acid, Group III- SmearClear, Group IV- MTAD and Group V- normal saline. Subsequent to irrigation, all samples were rinsed, dried and sectioned longitudinally for evaluation of the smear layer removal under scanning electron microscope (2000X). Data were statistically analyzed by two-way analysis of variance and Tukey’s post hoc test with statistical significance set at p< 0.5.Results: The result showed that SmearClear was the most efficient in removing the smear layer. However, etidronic acid was found inferior than both SmearClear and MTAD.Conclusion: Chelators are essential for complete smear layer removal in association with organic solvent. Keywords ● Etidronic Acid  ● MTAD  ● SmearClear  ● Smear Layer  ● Scanning Electron Microscope