Introduction: In vitro studies show that fluoride varnishes (FVs) differ significantly in their ability to remineralize and fluoridate enamel caries lesions, as, respectively, measured by percent surface microhardness recovery (%SMHr) and enamel fluoride uptake (EFU). However, there is a need to confirm these findings in clinically relevant conditions. Methods: This in situ study adopted a five-leg crossover design. In each leg, 28 subjects wore their mandibular partial denture with two previously demineralized enamel slabs treated with one of the following FV (selected based on our previous in vitro data): Vanish™ (high-%SMHr, low-EFU), Flor-Opal® (low-%SMHr, high-EFU), Enamel-Pro® (high-%SMHr, high-EFU), PreviDent® (generic, commercial reference), or negative control (no varnish). After 3 days, specimens were wrapped in gauze to allow plaque accumulation on the enamel. Toothbrushing of natural teeth was performed twice/day with F-free toothpaste. After 14 days, enamel specimens were collected and analyzed (%SMHr and EFU). Data were analyzed by ANOVA models suitable for crossover (alpha = 0.05). Results: Vanish™ had a significantly higher %SMHr; other varnishes did not differ from each other and had higher %SMHr than the control. EFU was significantly lower for the control than for all other treatments; Flor-Opal® had significantly lower EFU than Vanish™ and PreviDent®. Neither %SMHr nor EFU in vitro data could predict in situ results, although better approximation was observed for %SMHr. Conclusion: All tested FV could remineralize enamel; however, they presented different efficacies. Comparative clinical trials are warranted to confirm these results. Adequate in vitro tests are necessary to predict the clinical efficacy of FVs.

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