AbstractTo analyse clinical studies investigating coating agents such as sealants and other bonding materials to prevent the initiation or inhibit the progress of white spot lesions (WSL) during orthodontic treatment with fixed appliances. Electronic databases (Pubmed, CENTRAL, EMBASE) were screened for studies. No language restrictions were applied. Study selection, data extraction and quality assessment were done in duplicate. Primary outcome included assessment of WSL with visual-tactile assessment and/or laser fluorescence measurements. Twenty-four studies with 1117 patients (age: 11–40 years) and 12,809 teeth were included. Overall, 34 different sealants or bonding materials were analysed. Fourteen studies analysed fluoride and 14 studies non-fluoride releasing materials. Meta-analysis for visual tactile assessment revealed that sealants significantly decreased the initiation of WSL compared to untreated control (RR [95%CI] = 0.70 [0.53; 0.93]; very low level of evidence). Materials releasing fluoride did not decrease initiation of WSL compared to those with no fluoride release (RR [95%CI] = 0.84 [0.70; 1.01]; very low level of evidence). For laser fluorescence measurements no meta-analysis could be performed. The use of sealants seems to be effective in preventing the initiation of post-orthodontic WSL. Furthermore, there is no evidence supporting that fluoride-releasing sealants or bonding materials are more effective than those without fluoride release. No gold standard prevention strategy to prevent WSL during treatment with fixed orthodontic appliances has been established yet. However, based on only a limited number of studies the use of sealants seems to be effective in preventing the initiation of post-orthodontic WSL.