Background: The purpose of the endodontic treatment is to achieve thorough debridement of the root canal irregularities in the canal systems, narrow isthmi, and apical deltas prevent complete debridement by mechanical instrumentation alone. Thus, a variety of irrigants along with the mechanical instrumentation are required to clean and shape the root canals before obturation. Aims and Objectives: The aim and objective of the study was to compare and evaluate the smear layer removal efficacy of different final irrigants from the coronal, middle, and apical third of the root canals of primary teeth using field-emission scanning electron microscopy. Materials and Methods: Sixty therapeutically extracted human single-rooted primary teeth were prepared by step-back technique. Prepared teeth were randomly divided into six groups (n = 10): MTAD (Group I), TetraClean (Group II), QMix (Group III), 0.9% normal saline (Group IV), coconut water (Group V), and 5.25% NaOCl (GroupVI). After irrigation with final irrigants, the teeth were evaluated and assessed for the amount smear layer present under a field-emission scanning electron microscope using a score system criteria by Rome et al. Data obtained were analyzed using the Pearson's Chi-square test and McNemar–Bowker test. Results and Conclusions: Among the six irrigants QMix 2 in 1 showed the best smear layer removal efficacy, followed by 5.25% NaOCl, TetraClean, MTAD, coconut water, and the least efficacy was for normal saline.