Objectives: This study was conducted to compare between the effect non-invasive treatment modality using fluoride, Tri-Calcium Phosphate and nanohydroxyapatite based remineralizing agents versus micro-invasive treatment modality using Resinous and Resin modified glass ionomer Infiltrants materials on surface micro-hardness of incipient carious enamel lesions. Furthermore, the stability of these treatment options upon exposure to acidic challenge.Methods: A total of 60 sound human permanent molars were used in this study. The specimens were divided into six equal groups (10 teeth for each group) according to the treatment modality; Group (A0): Artificial saliva, Group (A1): fluoride, Group (A2): Tri-Calcium Phosphate, Group (A3): Nano Hydroxyapatite, Group (A4): Resin infiltrant and Group (A5): Resin modified glass ionomer infiltrant. The molars were decoronated and mounted in cylindrical self-cured acrylic resin molds with their buccal surface facing upwards. The buccal surface of each molar was polished using 400,600,800 and 1200 grit silicon carbide abrasive papers. A standardized window of 5mm × 3mm dimension was created on the buccal enamel surface of each specimen which demarcated by acid resistant nail varnish of different colors. To induce incipient carious enamel lesions, specimens were immersed in demineralizing solution at pH 4.5 for 72 hours at room temperature. All treatments were applied according to the manufacturers’ instructions. After application of the tested materials, all specimens were immersed in artificial saliva for two weeks. The specimens were finally subjected to acidic challenge using the same demineralizing protocol used for inducing caries-like lesions. The surface microhardness (SMH) of each specimen was assessed using Vickers micohardness tester, at baseline of sound untreated enamel (SMH/B), after demineralization (SMH/D), after treatment for two weeks (SMH/T) and finally, after exposure to acidic challenge (SMH/C). The percentage of surface microhardness recovery (%SMHR) and percentage of change in surface microhardness (%SMHC) were calculated. Results: The results of the current study revealed that both resin infiltrant based material and nanohydroxyapatite based remineralizing agent showed the highest statistically significant mean surface microhardness values and surface microhardness recovery percentage. Moreover, RMGI based infiltrant material and TCP based remineralizing agent showed statistically significant higher surface microhardnes recovery percentage compared to that of fluoride based remineralizing agent. Also, the artificial saliva showed the lowest statistically significant surface microhardness values and surface microhardness recovery percentage.On the other hand, all treatment modalities increased the resistance of enamel surface to demineralization upon exposure to acidic challenge. However, the fluoride based remineralizing agent followed by artificial saliva showed the lowest statistically significant surface microhardness values among the other treatment modalities.Conclusions: Under the limitations of the current study, the following conclusions could be derived:1.Non-invasive treatment modalities based on remineralization and micro-invasive treatment modalities based on resin infiltration are both viable options for treatment of incipient carious enamel lesions. 2.Resinous based infiltrant and Nano-hydroxyapatite remineralizing agent are the most effective treatment modalities for incipient carious enamel lesions.3.Although some demineralization has occurred with all treatment modalities upon exposure to acidic challenge, still they provided potential for inhibiting further progression of incipient carious enamel lesions.Further investigations: Since the nanohydroxyapatite based remineralizing agent showed equal efficiency to the resin infiltrant treatment option, then it is advised to perform further research work to clarify the capability of the nanohydroxyapatite to mask the color of white spot lesions. This might make it a more conservative treatment option.