ObjectiveThis was a randomized, double-blind, parallel, placebo-controlled in vivo study investigating the protective potential of a titanium tetrafluoride/ sodium fluoride (TiF4/NaF) solution compared to its respective positive and negative controls under an in vivo model, as well as the perception of participants regarding the use of this experimental solution. MethodsAfter the ethics approval and the selection procedures, 33 participants were divided into three treatments: TiF4/NaF solution (500 ppm F, pH 4.4); AmF/NaF/SnCl2-mouthwash (500 ppm F, pH 4.5) and water (pH 7.0) (n = 11). After professional cleaning, the participants rinsed with one of the solutions for one minute and waited two hours for the erosive challenge. The erosive solution (1 % citric acid, pH 2.5) was applied for 10 s on each central incisor (enamel area: 4 mm2) and collected for calcium analysis using III Arsenazo colorimetric method. The Ca2+ release data were compared using Kruskal-Wallis/ Dunn tests (p < 0.05). ResultsTeeth treated with both fluoride solutions released less calcium into the acid (median and interquartile interval: TiF4/NaF – 0.45/0.19 mM and AmF/NaF/SnCl2 – 0.46/0.15 mM Ca2+, p = 0.99) compared to the negative control (1.12/0.42 mM Ca2+, 60 % reduction, p < 0.0006). For both F solutions, only one participant per group reported unpleasant taste. Four participants belonging to AmF/NaF/SnCl2-mouthwash reported burning sensation post-rinse, while only one participant described such feeling after TiF4/NaF rinsing. ConclusionThe experimental TiF4/NaF solution was as effective as the commercial AmF/NaF/SnCl2-mouthwash in protecting enamel against erosive demineralization with a good acceptability by the participants.