Objectives: To assess the performance of a novel resin-modified glass-ionomer cement (pRMGIC) bonded to various tooth tissues after two-time intervals. Methods: 192 sound human molars were randomly assigned to 3 groups (n = 64): sound enamel, demineralised enamel, sound dentine. Sixty-four teeth with natural carious lesions including caries-affected dentine (CAD) were selected. All substrates were prepared, conditioned and restored with pRMGIC (30% ethylene glycol methacrylate phosphate (EGMP, experimental), Fuji II LC (control), Fuji IX, and Filtek™ Supreme with Scotchbond ™ Universal Adhesive. Shear bond strength (SBS) was determined after 24 h and three months storage in SBF at 37C. The debonded surfaces were examined using stereomicroscopy and scanning electron microscopy (SEM). Multivariate Analysis of Variance (MANOVA), Bonferroni post hoc tests (alpha=0.05) and independent T-tests were used for multifactorial data analysis. Results: The hydrophilicity and functionality of EGMP enhanced the bond strength of the pRMGIC to different substrates after 24 h and 3 months as compared to F2LC (p<0.05). Adhesive failures were found to decrease with pRMGIC and integration into exposed enamel prisms and dentine tubules was observed with SEM. Ageing enhanced bond strength of pRMGIC to all substrates but was statistically significantly only in sound dentine. The SBS of pRMGIC was higher with sound vs. demineralised enamel at both time periods (p<0.001), while it was higher to CAD initially and to sound dentine post-storage (p = 0.004). Conclusions: pRMGIC exhibited enhanced bonding performance to various tooth tissues with an ability to seal exposed enamel prisms and dentine tubules. Clinical significance: pRMGIC is a promising material exhibiting long-lasting bonded-tooth interfaces, for its use in minimally invasive reparative techniques