Objectives: 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 = 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 1st 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 (+/- SD) enamel loss (mu m) for groups 1-4 on day 3 was 2.15 +/- 0.35(a), 1.20 +/- 0.22(b), 0.95 +/- 0.19(b) and 1.98 +/- 0.32(a); on day 7 was 3.05 +/- 0.40(a), 2.07 +/- 0.32(b), 1.36 +/- 0.33(c) and 3.69 +/- 0.27(d) respectively. For acid-softened enamel at baseline, enamel loss on day 3 was 3.16 +/- 0.19(a), 2.17 +/- 0.14(b), 1.70 +/- 0.11(c) and 3.04 +/- 0.19(a); on day 7 was 3.92 +/- 0.25(a), 3.07 +/- 0.13(b), 2.09 +/- 0.15(c) and 3.87 +/- 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.