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Orthodontic treatment with fixed appliances is considered a risk factor for the development of white spot caries lesions (WSL). Traditionally, brackets are bonded to the buccal surfaces. Lingual brackets are developing rapidly and have become more readily available. Buccal surfaces are considered to be more caries prone than lingual surfaces. Furthermore, lingual brackets are shaped to fit the morphology of the teeth and seal almost the entire surface. In the present study we tested the hypothesis that lingual brackets result in a lower caries incidence than buccal brackets. We tested this hypothesis using a split-mouth design where subjects were allocated randomly to a group receiving either buccal or lingual brackets on the maxillary teeth and the alternative bracket type in the mandible. The results indicate that buccal surfaces are more prone to WSL development, especially when WSL existed before treatment. The number of WSL that developed or progressed on buccal surfaces was 4.8 times higher than the number of WSL that developed or progressed on lingual surfaces. When measured using quantitative light-induced fluorescence (QLF), the increase in integrated fluorescence loss was 10.6 times higher buccally than lingually. We conclude that lingual brackets make a difference when caries lesion incidence is concerned.