Introduction:Globally, the increased prevalence of dental caries in children makes the need for dental remineralizing agents necessary. To the best of our knowledge there are a few published clinical trials on the effectiveness of nano-re-mineralizing agents but without comparing between them. Objectives: To compare nano-silver fluoride (NSF), nano-hydroxyapatite (n-HAP) and sodium fluoride (NaF) varnishes in prevention and arrestment of initial enamel caries on young permanent teeth. Material and methods: One hundred and fifteen children with ages ranging from 7 to 10 years were randomly divided into three groups: the NSF group (n = 39), the n-HAP group (n = 37) and the NaF group (n = 39). The clinical evaluation of dental surfaces was done by one masked examiner using ICDAS II to detect the number of new and arrested initial lesions. Varnish application was done annually for NSF, but it was done biannually for n-HAP and NaF. This was followed up at 3, 6 and 12-month intervals. The Kruskal-Wallis test was used to compare the groups. Results: After a follow-up period of 12 months, the NSF group had a significantly lower median number of new carious lesions, 1 (0), than the n-HAP group, 2 (3), with p = 0.01. There were significantly more arrested lesions in both NSF and NaF than in n-HAP at all visits, with p = 0.003, 0.01 and 0.002. At the level of children, the NSF group had the lowest number of children who were affected by new caries (23.1%) and the highest number of children who have arrested initial caries (87.2%). Conclusions: Annual application of NSF varnish might be recommended as an effective method of dental caries prevention and treatment of initial caries lesions.