BackgroundProfessionally applied topical fluoride preparations have been commonly used and have proven to prevent dental decay. Alternative preparations that provide further benefits may be of interest to investigate. This study aimed to investigate the effect of experimental nano silver fluoride (NSF) formulation compared to commercial sodium fluoride varnish (FV) on prevention of in vitro demineralization of initially sound enamel in primary teeth.MethodsForty-eight extracted/exfoliated sound molars were sectioned buccolingually into 96 specimens then assigned randomly into two equal groups. Each group was further subdivided into two equal subgroups (Ia: NSF, IIa: FV, Ib and IIb as negative controls). The test materials were applied, then all the specimens were subjected to a demineralization pH cycling model for 7 days. Specimens were examined for surface microhardness using Vickers microhardness device and lesion depth was evaluated by polarized light microscope using image J 1.46r software. Data were analyzed using paired t-test, independent t-test, and Mann Whitney U test.ResultsThe test materials were significantly superior to their negative controls, (P < 0.001) and comparable to each other, (P > 0.05) regarding microhardness and lesion depth. In comparison to FV, NSF showed lower yet statistically insignificant percent increase in microhardness and decrease in lesion depth, (P = 0.81, 0.86, respectively). Qualitative evaluation revealed that both agents reduced the lesion depth formation.ConclusionNSF showed similar effect to that of FV in limiting in vitro enamel demineralization caused by acidic challenge. Hence, it could be regarded as a promising alternative preventive agent in primary teeth.