Aim: The aim of this study was to evaluate the efficacy of a novel fluoride varnish (NFPV, Fluor Protector S) in preventing development of white spot lesions in adolescents undergoing treatment with fixed orthodontic appliances. Material and methods: 185 patients aged between 12 and 18 years planned for orthodontic treatment with fixed appliance were randomized into varnish or placebo group. The varnish group received a varnish with the active ingredient ammonium fluoride and the placebo group received a similar varnish but without ammonium fluoride. All patients received treatment with fixed orthodontic appliance in the upper arch for a period of more than one year, and before bonding all patients had three intra-oral photos. Varnish in both groups was applied on the maxillary anterior teeth and premolars during every check-up at the orthodontic clinic (every 6 weeks). After debond, the composite on the teeth was carefully removed using carbide bur and three new intra-oral photos were taken. Finally, white spot lesions (WSL) were evaluated and scored on a monitor in a dark room using Gorelick scoring index. Results: 66 patients of the 185 patients were debonded and represent the final number of patients included in present master thesis. The incidence of WSL after debond was 19.9% in the test group and 18.1% in the placebo group, respectively. No statistically significant difference between the groups was recorded. Conclusion: Based on the limited amount of the patients in present master thesis, the null hypothesis was confirmed, there is no additional benefit to apply ammonium fluoride varnish during treatment with fixed orthodontic appliance to reduce the incidence of WSL.