Background: This study aims to investigate the efficacy of ER, CR: YSGG laser combined with functionalized tricalcium phosphate (fetch) exclusively from Cilantro White Varnish in preventing of enamel caries. Materials and Methods: Freshly extracted fifty sound upper first premolars teeth were divided into five groups, each group of ten samples. Group (C): only washed with deionized water. Group (V): functionalized tricalcium phosphate (fTCP) exclusively from Clinpro White Varnish. Group (L1): Er,Cr:YSGG laser (0.25watt, 2.8 J/cm2, 20 Hz, 11% air, 0% water) was irradiated. Group (V/L1): First Cilantro White varnish was applied then Er,Cr:YSGG laser. Group (L1/V): Er,Cr:YSGG laser was irradiated followed by Clinpro White varnish. Then, the pH cycling model was used to induce artificial caries. The effect was studied using Vickers microhardness test and the obtained results were statistically analyzed. The surface morphology was also studied by scanning electron microscopy. Results: There was decreasing in surface microhardness in all groups due to the demineralization. Statistically there was no significant difference between groups of combinations and group of varnish while all of these groups had a highly significant resistance against microhardness loss. The least value of surface microhardness belonged to the control group and laser group. Morphological changes of enamel surfaces were in relation with increasing of enamel resistance to demineralization. Conclusions: The impacts on enamel resistance to demineralization and reducing its solubility seem to indicate that there is no benefit in using Er,Cr:YSGG laser at 0.25watt alone or as a pretreatment and post treatment for fTCP varnish over using fTCP varnish alone.