Objective: To evaluate the effect of resin infiltration (RI) prior to at-home bleaching on hydrogen peroxide (HP) penetration into the pulp chamber, color change, and enamel morphology in human teeth with sound enamel or white spot lesions (WSLs), using different RI protocols.

Materials and methods: Sixty human premolars were randomly allocated into six groups (n = 10), according to enamel substrate (sound/WSLs) and treatment: at-home bleaching with 16% carbamide peroxide only (CP); RI with one prior acid-etching application followed by at-home bleaching (RI1/CP); and RI with three prior acid-etching applications followed by at-home bleaching (RI3/CP). HP penetration was quantified by UV-Vis spectroscopy. Color change was evaluated using a digital spectrophotometer (ΔE₀₀; WI_D). Enamel surface morphology was analyzed by SEM (α = 0.05).

Results: RI significantly reduced HP penetration into the pulp chamber compared with CP alone, with reductions of over 90%, regardless of enamel substrate or RI protocol. Without RI, artificially induced WSLs showed greater HP diffusion than sound enamel (p < 0.05). Color outcomes (WI_D) were comparable between RI-treated and sound teeth. SEM showed more homogeneous surfaces after RI.

Conclusions: RI prior to at-home bleaching with 16% CP reduced HP penetration into the pulp chamber without compromising bleaching efficacy. Comparable color outcomes were achieved in teeth with WSLs, irrespective of prior acid-etching applications.

Clinical significance: When combined with at-home bleaching, RI may reduce HP diffusion into the pulp chamber and improve esthetic integration of artificially induced WSLs through optical masking. However, these findings are based on an in vitro model and should be interpreted with caution regarding clinical outcomes.