Objective: To analyze the staining and color changes of a resin infiltrant system used for management of white spot lesions (WSLs). Materials and Methods: WSLs were artificially created on left buccal halves of 48 extracted human teeth. These sites were then treated with resin infiltration (RI) while the right halves of the teeth remained as nonresin (NRI) areas. Six groups were formed (n ¼ 8 teeth/group) and were exposed to the following: red wine, coffee, orange juice, combined staining agents, accelerated aging, and distilled water for 1 week. The teeth were then polished with a prophy cup and polishing paste. Color properties were assessed using a spectrophotometer at baseline (T0), after each exposure (T1), and after polishing (T2). Color difference (DE*) was calculated between each time point for both halves of the teeth (RI and NRI). Data were analyzed with a two-way analysis of variance with presence of resin infiltration and staining agents as the main effects for each time point pair. Multiple comparisons were made with a Bonferroni post hoc test. The level of significance was set at P , .05. Results: The red wine and combined staining agent groups caused the greatest color change between all intervals (P , .05). Significant interactions were recorded between resin infiltration application and staining agents at all time periods (P , .05). The presence of resin infiltration as a main effect did not affect color change between T0 and T2 (P . .05). Conclusions: RI areas showed higher staining susceptibility than did NRI areas. However, prophylaxis had a strong effect on reversing the discoloration of both RI and NRI areas. (Angle Orthod. 2016;86:900-904)