This single-center, randomized, placebo-controlled, four-treatment, four-period crossover study compared the enamel remineralization effects of low- and medium-abrasivity gel-to-foam toothpastes and a reference toothpaste (all 1,450 ppm fluoride as NaF) versus placebo toothpaste (0 ppm fluoride) using a short-term in situ erosion model. Subjects (n = 56) wearing a palatal appliance holding acid-softened bovine enamel specimens brushed their teeth with the test toothpastes. Thereafter, the specimens were removed for analysis of percent surface microhardness recovery (%SMHR) and percent relative erosion resistance (%RER) at 2, 4, and 8 h. Both low- and medium-abrasivity gel-to-foam fluoride toothpastes and the reference toothpaste provided significantly greater %SMHR than placebo at all assessment time points (all p < 0.05). No statistically significant difference of %SMHR was observed between the fluoride treatment groups at any time point. Similarly, all fluoride products provided significantly superior %RER versus placebo (all p < 0.0001), whereas no significant difference of this parameter was noted between the fluoride treatment groups. Increasing numerical improvements of %SMHR and %RER were observed in all four treatment groups over time (2, 4, and 8 h). The present in situ model is a sensitive tool to investigate intrinsic and fluoride-enhanced rehardening of eroded enamel. All three fluoride toothpastes were more efficacious than placebo, and there were no safety concerns following single dosing in this short-term in situ model.