BackgroundClinicians always experience dilemmas while choosing the type of pit and fissure sealant and the method of enamel preparation before the application of sealant. This study was accomplished using the unfilled and filled types of resin sealant deploying three different techniques of enamel preparation.Aim and objectiveTo do a comparative analysis of unfilled and filled sealants by deploying three techniques of enamel preparation.Materials and methodsThe total number of 60 extracted teeth were divided into 3 groups, each containing 20 samples. Conventional acid etching of enamel was labeled as (group I), laser application as (group II), and fissurotomy bur (group III). The samples of group I were prepared by conventional acid etching, the group II was subjected to Er:YAG lasing, while in group III fissurotomy followed by acid etching was done. The sealant placement was done using split tooth design in all the samples. Dye penetration using 5% methylene blue was used for microleakage assessment.ResultsThe highest microleakage was found with Gr. II whereas Gr. I exhibited the least microleakage. No statistical difference was observed between the unfilled and filled sealant (p = 0.652).ConclusionConventional acid etching alone or with fissurotomy weighed up appropriate option regardless of the type of sealant material used.Clinical significanceIn regard to the selection of material and proper technique of enamel preparation, this study will be useful to clinicians.How to cite this articleShingare P, Chaugule V. An In Vitro Microleakage Study for Comparative Analysis of Two Types of Resin-based Sealants Placed by Using Three Different Types of Techniques of Enamel Preparation. Int J Clin Pediatr Dent 2021;14(4):475–481.