Purpose: To evaluate the influence of a 2% chlorhexidine solution (CHX) on the bond strength and nanoleakage of two self-etching adhesive systems on demineralized dentin over a 12-month period. Materials and Methods: The middle dentin from sound third molars was exposed and demineralized in vitro. Twelve groups were formed using different adhesive systems (Clearfil Protect Bond [PB], Clearfil SE Bond [SE]) dentin treatment (with or without CHX application), and water-storage times (24 h, 6 and 12 months). Composite resin cylinders were bonded to the prepared dentin, and these specimens underwent microshear bond strength (µSBS) testing and nanoleakage evaluation. µSBS data were submitted to a three-way ANOVA and Tukey's test. The failure mode and nanoleakage were analyzed descriptively by score. Results: There was a statistically significant interaction only between the adhesive system and CHX, and adhesive system and water-storage times. SE showed the lowest µSBS just at 24 h water-storage time regardless of CHX. A significant decrease in µSBS values after 6 months of water storage occurred in all of the groups and was maintained until 12 months. Adhesive failure increased with storage time. All groups showed nanoleakage at the resin/dentin interfaces and an increased silver deposition was noticed after 6 and 12 months of water storage. The highest percentages of nanoleakage were found in CHX groups. Conclusion: CHX did not interfere with µSBS values for either self-etching adhesive system, but water storage did. Bond strength decreased for both adhesive systems after 6 and 12 months, regardless of CHX application. Nanoleakage increased with water-storage time and with CHX application. Keywords: microshear bond strength, chlorhexidine, adhesive systems, bond degradation, nanoleakage, cariesaffected dentin