Introduction: Topical fluoride therapy has proven benefits in the prevention of demineralization. Tooth enamel has shown a great potential for remineralization with an application of topical fluorides if administered at an appropriate time. In an effort to find an effective remineralizing agent, a novel fluoride agent silver diamine fluoride (SDF) has emerged as a potent caries arresting as well as caries preventing agent. Aim and objective: The present study was aimed at determining the primary tooth enamel resistance to demineralization after topical application of three fluoride agents SDF, APF, and NaF. Materials and methods: Enamel specimens were prepared from 40 caries-free primary molars. These specimens were randomly allocated into three groups of 10 specimens each and they were treated by different topical fluorides namely: Group I–SDF, group II–Acidulated phosphate fluoride (APF), group III–Sodium fluoride. Three enamel specimens from each group were placed on custom-made acrylic blocks with 5 × 5 mm of an exposed window for scanning electron microscope (SEM) evaluation and rest of the specimens were ground into a fine powder for X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis. The tooth blocks and treated samples were subjected to the demineralization process for 168 hours. They were then qualitatively assessed to evaluate their resistance to demineralization using SEM, XRD, and FTIR. Results and conclusion: Morphologically, the enamel of all groups specimens was mostly smooth with some groves and microporosities. Chemically, the Ca/P molar ratios of all groups were similar with slight variations. Structurally, the crystalline phases found in enamel by powder XRD were hydroxyapatite and carbonate apatite; and there was a higher amount of incorporated type B carbonate than type A carbonate as evidenced by FTIR. The study concludes that topical application of a 38% SDF solution can inhibit demineralization of enamel.