OBJECTIVES: To evaluate the remineralizing effect of varnishes containing different concentrations of S-PRG filler or sodium fluoride on enamel caries lesions. METHODS: Enamel specimens were obtained from bovine incisors, flattened and polished. Half of the surface was protected, and artificial caries lesion was created in the unprotected area. They were assigned into six groups (n=20) according to the varnish applied: four containing S-PRG filler with different concentrations (10%, 20%, 30% and 40% w/w), one containing 5% sodium fluoride (5%NaF) as positive control, and one without treatment as a negative control (NC). Varnishes were applied on specimen's caries-affected surface and removed after 24 h. Varnish application and pH cycling (8 days) were performed twice. Cross-sectional microhardness was measured (10-100 µm depth). Knoop microhardness percentage (KHN%) of caries affected/treated area in relation to the sound enamel area at the same depth was calculated. The area under the curve (AUC) and the ΔAUC were also calculated. Statistical analysis was performed by two-way ANOVA for KHN% and one-way ANOVA for ΔAUC, followed by Tukey test (α=5%). RESULTS: Significant differences were found for the factors "treatment" (p=0.0001) and "depth" (p=0001). For the factor "treatment", the results of the Tukey test were: NC-62.2(10.3)a, 10%S-PRG-69.2(9.3)b, 20%S-PRG-71.8(9.7)bc, 30%S-PRG-74.5(9.4)c, 5%NaF-79.6(8.7)d, 40%S-PRG-85.6(8.4)e. In relation to ΔAUC, significant differences were observed among the groups (p=0.0001) and better results for 40% S-PRG and 5%NaF. CONCLUSIONS: The varnish containing 40% S-PRG fillers was the most effective to promote the enamel caries remineralization, followed by the one containing 5% sodium fluoride. CLINICAL SIGNIFICANCE: The varnish containing 40% of S-PRG fillers represents an alternative for initial enamel caries remineralization, since it was more effective than the conventional 5% NaF based product.