ObjectivesTo evaluate the erosion preventive effect of 38 % silver diamine fluoride (SDF) solution in enamel and dentin of human permanent teeth. MethodsNinety enamel and ninety dentin blocks were prepared from permanent molars and allocated into three groups. Gp-SDF received a one-off application of 38 % SDF solution. Gp-SNF received a one-off application of a solution containing 800 ppm stannous chloride and 500 ppm fluoride. Gp-DW received a one-off application of deionized water. The blocks were submitted to acid challenge at pH 3.2, 2 min, 5 times/day for 7 days. All blocks were immersed in human saliva between cycles for one hour. The crystal characteristics, percentage of surface microhardness loss (%SMHL), surface loss, and elemental analysis and surface morphology were examined by X-ray diffraction (XRD), microhardness test, non-contact profilometry, and energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM), respectively. Data of%SMHL and surface loss were analyzed by one-way ANOVA. ResultsXRD spectra revealed that fluorapatite and silver compounds formed in Gp-SDF, while fluorapatite and stannous compounds formed in Gp-SNF. Gp-DW presented only hydroxyapatite. The median (interquartile range) of%SMHL in Gp-SDF, Gp-SNF and Gp-DW were 27.86(3.66), 43.41(2.45), and 46.40(3.54) in enamel (p< 0.001), and 14.21(1.57), 27.99(1.95), and 33.18(1.73) in dentin, respectively (p < 0.001). The mean (standard deviation, μm) of surface loss of Gp-SDF, Gp-SNF, and Gp-DW were 2.81(0.59), 4.28(0.67), and 4.63(0.64) in enamel (p < 0.001) and 4.13(0.69), 6.04(0.61), and 7.72(0.66) in dentin, respectively (p < 0.001). SEM images exhibited less enamel corruption and more dentinal tubular occlusion in Gp-SDF compared to Gp-SNF and Gp-DW. EDS analysis showed silver was detected in Gp-SDF while stannous was detected in the dentin block of Gp-SNF. Conclusion38 % SDF yielded superior results in protecting enamel and dentin blocks from dental erosion compared to SNF and DW. Clinical significanceTopical application of 38 % SDF is effective in preventing dental erosion in human enamel and dentin.