Objectives: The aim of this study was to evaluate the efficacy of MI Paste Plus(GC America), SootheRx(Omni), and Fluoride toothpaste in retarding demineralization of enamel and dentin around amalgam restorations in vitro. Methods: 60 Extracted human 3rd molars were selected after which a Class V restoration was placed at the CEJ and the teeth were varnished leaving a 1mm window around the restoration in enamel and dentin. The teeth were randomly divided into five treatment groups: Control(C), MI Paste Plus(MI), SootheRx and Fluoride(1000 ppm)(NF), SootheRx(N), and ControlRx(F). The teeth were treated twice daily for 30 minutes between cycling in de/remineralization solution [treatment, 6 hours demineralization (2.2 mM Calcium, 2.2 mM Phosphate, 0.5 M Acetate buffer, pH 4.5), treatment, then 17 hours remineralization (1 mM/L CaCL2, 3 mM/L NaH2PO4, 20 mM/L NaHCO3, pH 7.0]. This cycling regimen continued for 14 days. Teeth were sectioned into 3 sections with a Silverstone microtome approximately 130 um thick and analyzed with polarized light microscopy. Results: C, MI, and N were statistically identical in both enamel and dentin lesion depth. F and NF showed significant less demineralization than C, MI, and N in enamel. In dentin NF was significantly different from C, MI, and N. F had significantly less demineralization than C, MI, N, and NF in dentin. Significance level was P<0.05. Conclusion: In this in vitro model treatments NF and F showed significant inhibition of demineralization in enamel and dentin when compared to C, MI, and N. This research was supported by NIDCR, grant #T32 DEO14678-04. Treatments | Enamel lesion depth(um) | Dentin lesion depth (um) | C | 145.80 | 176.13 | MI | 137.75 | 172.23 | N | 134.16 | 171.74 | F | 53.55 | 90.50 | NF | 65.50 | 131.34 | |