The aim of this laboratory and clinical study is to determine the reliability of the flowable nanocomposite Filtek Supreme XTE (FL) for the adhesion of orthodontic retainers, compared to highly filled orthodontic resin Transbond XT (XT). Portions of a round section multistranded wire (Ortosmail Krugg) were bonded to 40 bovine incisors with Scotchbond Universal in total-etch modality. For group one (XT, 20 samples), the orthodontic resin was used, whereas in group two (FL, 20 samples), the flowable one. Specimens were placed into a universal testing machine which applied a shear force on retainers with a crosshead speed of one/minute. Shear bond strength (SBS) and adhesive remnant index (ARI) scores were calculated. In the clinical trial, 100 patients requiring a canine-to-canine palatal and lingual retainer were randomly divided into two groups, according to the resin used for bonding procedure: the orthodontic in group one (XT, 50 participants) and the flowable in group two (FL, 50 participants). Monthly visits were carried out over a 24-month follow up to assess any detachment occurring on teeth of both arches. All data were submitted to statistical analysis. In vitro, FL reported a significant lower mean SBS, whereas no significant differences in ARI were reported between the two groups which both showed a major frequency of scores "1" and "2". At the end of the 24-month follow up, FL reported significantly higher failure rates in both arches besides a significantly lower survival rate starting from the sixth month after retainers bonding. According to the results assessed in vitro and clinically, XT would be preferable to FL when performing retainers bonding procedure.