To compare in vitro the effect of a toothpaste containing fluoride (F), calcium silicate (CaSi) and sodium phosphate salts to conventional toothpaste (NaF) on human enamel specimens submitted to erosive and abrasive challenges. Methods: 48 sound and 48 enamel samples pre-treated with 1% citric acid were divided into 4 groups (n ¼ 12): Group 1-Non-fluoride toothpaste; Group 2-NaF toothpaste (1450 ppmF); Group 3-CaSi toothpaste (1450 ppmF; MFP); Group 4-Erosion only. The samples were subjected to pH cycling (3 cycles/day; 90s; 1% citric acid, pH 3.6) and to abrasion for 7 days. After the 1 st and the last cycle, they were submitted to abrasion (15s, 1.5N load), using a brushing machine, soft toothbrush and toothpaste slurry (1:3; 15ml/sample) and then immersed in the slurry for 45s. Samples were immersed in artificial saliva between the challenges. Enamel loss was evaluated using profilometry on days 3 and 7. Data were analysed by ANOVA and Tukey's test (p < 0.05). Results: For sound enamel at baseline, mean (AESD) enamel loss (μm) for groups 1-4 on day 3 was 2.15 AE 0.35 a , 1.20 AE 0.22 b , 0.95 AE 0.19 b and 1.98 AE 0.32 a ; on day 7 was 3.05 AE 0.40 a , 2.07 AE 0.32 b , 1.36 AE 0.33 c and 3.69 AE 0.27 d respectively. For acid-softened enamel at baseline, enamel loss on day 3 was 3.16 AE 0.19 a , 2.17 AE 0.14 b , 1.70 AE 0.11 c and 3.04 AE 0.19 a ; on day 7 was 3.92 AE 0.25 a , 3.07 AE 0.13 b , 2.09 AE 0.15 c and 3.87 AE 0.25 a respectively. Conclusions: Both F toothpastes led to significantly higher enamel protection from short-term erosion and abrasion in comparison to the non-F toothpaste and erosion only. In the longer term, CaSi toothpaste conferred significantly higher protection than NaF toothpaste. Clinical significance: The results showed that for the longer term the CaSi toothpaste provided significantly higher protection than the NaF toothpaste, which indicates a good potential of the former to help prevent erosive tooth wear.