INTRODUCTION: Enamel deproteinization before acid etching can be used as a method to improve and enhance the sealant's retentive and sealing ability OBJECTIVES: To assess and compare the sealant shear bond strength and nanoleakage after placement on etched enamel with and without prior deproteinization. MATERIALS AND METHODS: Eighty extracted sound human permanent teeth were selected. These were randomly divided into two groups according to the enamel treatment methods, where group A (experimental group): deproteinization prior to acid etching and group B (control group): acid etching without deproteinization. Each group was further subdivided equally into two subgroups (n=20) according to the test used whether shear bond strength and nanoleakage respectively. Shear bond strength test: Shear bond strength was measured using universal testing machine. Mode of failure of each specimen was determined using stereomicroscope. Nanoleakage test: Sealed teeth were then thermocycled, immersed in 50% silver nitrate solution for 24 hours, sectioned and evaluated quantitatively using energy dispersive x-ray spectrometer (EDX) and qualitatively using scanning electron microscope (SEM). Data were collected, tabulated and statistically analyzed using Mann-Whitney U test (P<0.05), chi square test and Post-hoc analysis. RESULTS: The rate of sealant shear bond strength was similar between the two groups (P=0.678), but the rate of sealant nanoleakage was significantly lower in the enamel deproteinization group (P<0.001) than in the control group. CONCLUSIONS: Deproteinization method prior to enamel acid etching improved shear bond strength and sealing ability of sealants..