This study examined the effectiveness of resin infiltration in inhibiting microleakage from artificial white-spot lesions (AWL) in enamel. Fifty sound extracted premolars were selected and randomly divided into five groups (n = 10 each). Group 1 included sound teeth. In contrast, an AWL was created in all specimens in groups 2 to 5, as follows-Group 2: AWL with no treatment; Group 3: AWL treated with resin infiltration; Group 4: AWL treated with resin infiltration and 5,000 cycles of thermocycling; Group 5: AWL treated with resin infiltration and 10,000 cycles of thermocycling. All specimens were then coated with nail varnish, except for a 4 × 4 mm2 area on the buccal surface (the measurement area), immersed in 2% methylene blue solution, and sectioned buccolingually. Microleakage was evaluated with a stereomicroscope. Data were analyzed by using the Kruskal-Wallis test and Bonferroni post-hoc correction. Application of resin infiltrant reduced microleakage in AWL. No microleakage was seen in Group 3, and differences between Groups 3, 4, and 5 were not significant (P > 0.05). The resin infiltration technique appears to aid in sealing enamel AWL and may help provide long-term protection against microleakage in enamel AWL.