This study aimed at evaluating in vitro the effect of one year brushing with 10 wt. % nano- hydroxyapatite (n-HAp) modified toothpaste on surface roughness and micro-shear bond strength (µ-SBS) of enamel to resin composite restoration (Filtek Z350 XT Universal Restorative) using total-etch (TE), Adper Single Bond Plus Adhesive and self-etch (SE), Single Bond Universal Adhesive systems. Thirty human enamel/dentin slabs were prepared and divided according to the toothpaste into: control group (Signal Kids toothpaste) and test group (10 wt. % n-HAp ~20 nm modified Signal Kids toothpaste). Brushing was performed for one hour/day for 24 days. Roughness (Ra) was measured by the AFM for 10 brushed slabs. For μ-SBS evaluation, 20 brushed slabs were randomly subdivided into 2 subgroups/ group according to the adhesive system (control/TE, control/SE, test/TE and test/SE). Micro-cylinders of nano-filled resin composite were prepared. The μ-SBS test was performed by a universal testing machine. The mode of failure was evaluated by digital microscope and the morphological changes of the de-bonded surfaces were examined by the SE microscope. The data were statistically analyzed. The mean Ra (nm) values of the enamel brushed with unmodified toothpaste were not significantly different than those brushed with n-HAp modified toothpaste. Whereas, the mean μ-SBS (MPa) of the control (brushed with unmodified toothpaste) subgroups with either TE or SE were significantly lower than those of the test (brushed with n-HAp modified toothpaste) subgroups. Subgroups with SE adhesives exhibited predominantly adhesive failure mode, while predominance of mixed failures were detected for subgroups with TE adhesives. In conclusion, one year simulated brushing with 10 wt. % n-HAp modified toothpaste did not affect enamel roughness while it improved the bond strength to resin composite regardless of the adhesive system. However, the adhesive system type has an influential effect on the failure mode.