Purpose: To investigate the use of a cold atmospheric plasma (CAP) source in a clinically realistic endodontic procedure to enhance the bond strength of a dental adhesive in root canal restoration. Materials and Methods: CAP was generated by a handheld DBD-jet prototype specifically designed for biomedical applications. Extracted monoradicular teeth were standardized through crown sectioning and root canal shaping before being embedded in epoxy resin cylinders using a custom molding procedure designed to ensure the accurate alignment of the specimens. Afterwards, the dentin surface was conditioned according to different protocols including (or not, in controls) chelating agents (EDTA or IP6) and CAP treatment (180 s). Then a self-etch adhesive was applied, followed by a luting material to seal the root canal. Both materials were light cured. Tooth sections were obtained from coronal and middle portions of the root canal, and the push-out test was used to evaluate the bond strength between the adhesive and dentin. Results: Push-out results demonstrated that plasma treatment greatly improved (> twofold) the mechanical properties of the adhesive-dentin interface along the whole length of the root canal. Contact angle measurements and SEM analyses showed that plasma treatment facilitated adhesive permeation into dentinal tubules, hence enhancing the effects of the bonding procedure. Conclusions: Although investigations on long-term bond stability after CAP treatment and clinical studies are required, the present study indicates that CAP devices may be useful in clinical endodontic treatment. Keywords: adhesion enhancement, adhesion to dentin, adhesive, cold atmospheric plasma, dental restorations, endodontic adhesion, push-out bond strengths, root canal therapy