Purpose: To assess the enamel-protective potential of a newly devised adhesive patch for smooth enamel sealing. Materials and Methods: Approximal surfaces of 30 extracted molars were divided into three areas: the buccal thirds were treated with a flowable composite (Tetric Flow, Ivoclar Vivadent) and served as negative control sites, the lingual thirds were left untreated and served as positive control sites, and the middle thirds served as the test areas. This was sealed with either 1. a twofold application of an unfilled resin (Heliobond, Ivoclar Vivadent), 2. an adhesive prototype patch (Ivoclar Vivadent), or 3. an adhesive patch in combination with a flowable composite. After thermomechanical loading and demineralization in a microbial-based artificial caries chamber, demineralization depth was assessed using a confocal laser scanning microscope. Results: Negative control sites treated with the flowable composite showed no signs of demineralization. Areas treated with the patch showed no signs of demineralization, irrespective of whether it was used in combination with a flowable composite or directly bonded to the enamel. Caries-like lesions in untreated sites showed a mean depth of 134.3 ± 35.9 µm. Demineralization depth at sites treated with the unfilled resin was 76.2 ± 26.5 µm (p = 0.023). Conclusions: Under the conditions of the present study, the adhesive patch under investigation completely protected the underlying enamel from demineralization. This merits further study to assess its potential as an interproximal sealant. Keywords: caries, adhesive patch, CLSM, Streptococcus mutans, in vitro