Objective:The present study was conducted to compare microleakage in self-etching fissure sealants and conventional fissure sealants with total-etch or self-etch adhesive systems.Settings and Design:This experimental in vitro study was conducted on 60 healthy third molars extracted from humans. The first group received Acid etch + Clinpro sealant, the second group received Acid etch + Single bond 2 + Clinpro sealant, the third group received Single bond universal (self-etching bonding) + Clinpro sealant, and the fourth group received prevent seal self-etching sealant.Materials and Methods:An incision was made on the teeth after they were immersed in methylene blue 5%. The samples were then examined under a stereomicroscope and the dye penetration rate was measured based on the Williams and Winter criteria.Statistical Analysis Used:The Kruskal–Wallis and Mann–Whitney tests were used for data analysis in SPSS-18 (P < 0.05).Results:Group 1 which was treated with the conventional technique (acid + fissure sealant) had the highest rate of microleakage compared to Groups 2 and 3 (P < 0.001).Conclusion:The results showed that the use of bonding results in a significant reduction in the microleakage of fissure sealants. The microleakage caused when using self-etch fissure sealant was not different from that caused by the use of the conventional method.