OBJECTIVE This in-vitro study was done to evaluate the effects of two different seal materials, Duraflor™ and Enamel Pro(®) Varnish, on enamel demineralization adjacent to orthodontic fixed appliances. METHODS Seventy-two extracted solid premolars were allocated to three groups as one control and two study groups after brackets were placed and bonded with Transbond™ XT. The control group received no topical fluoride application after bonding, whereas in the study groups two fluoride varnishes, Enamel Pro(®) Varnish and Duraflor™ were applied on the teeth adjacent to brackets. All specimens were then immersed separately in demineralization solution for 96 hours at constant temperature. Demineralization of the enamel surface was evaluated quantitatively by cross-sectional microhardness testing: indentations were made at the edge of the bracket base (0 μm) and at 100 and 200 μm distant from it. In all of these positions, 5 indentations were made at 10, 20, 40, 70 and 90 μm of depths from the external surface of the enamel. RESULTS The results revealed that, Enamel Pro(®) Varnish and Duraflor™ group values are higher than the values of control group at every depth. The differences between the depths showed that the microhardness values decreased significantly when the depth increased. In the control group, more demineralization occurred in every indentation compared to the study group. CONCLUSIONS Duraflor™ and Enamel Pro(®) Varnish can be considered for use in clinic as an effective method to prevent or reduce demineralization during orthodontic treatment, especially in patients with poor oral hygiene.