The aim of the study was to verify whether subablative Er:YAG laser irradiation combined with fluoride application could provide a significantly greater inhibition of enamel demineralization histologically using Polarized light microscopy and to and to compare microhardness of enamel around orthodontic brackets after treatment by either fluoride, laser, or both. Material and methods: eighty freshly extracted premolars were randomly assigned to four groups after bonding: (A) control, (B) irradiated by Er: YAG laser& Voco Bifluoride 10™ varnish, (C) treated by Voco Bifluoride 10™ varnish, (D) irradiated by Er: YAG laser before pH cycle. Caries-like lesions were created by pH-cycling. At the end of the pH cycle, each group was divided into 2 equal sub-groups: first subgroup was prepared for microhardness test and examined under polarized light microscope, second subgroup received a second application of therapeutic agents then entered a second pH cycle for another 14 days then teeth were prepared for measuring surface micro hardness and examination under polarized light microscope. Results: group B showed decrease in percentage of lesion depth compared to control group by more than 70% and there was statistically significant difference between it and the other groups. Group D showed increase in percentage of lesion depth with marked loss of enamel surface compared to control group by 29% after 14 days and 9% after 28 days. Moreover group B showed the highest microhardness values and Group D showed the lowest values. Conclusion: In this in vitro study, laser and fluoride combination enhance the resistance of sound enamel around orthodontic brackets more effectively than Er: YAG laser application alone. Keywords: Demineralization, Er:YAG, Fluoride varnish, Microhardness, pH-cycling, Polarized microscopy