Stannous fluoride has been used as a chemotherapeutic agent for years to improve oral health. The benefits of stannous fluoride in controlling caries, plaque, and gingivitis are directly associated with its antimicrobial actions. Recently, a novel dentifrice was developed that combines stannous fluoride with an anticalculus agent, sodium hexa. metaphosphate. A series of independent evaluations were conducted to assess the long-lasting antimicrobial activity of stannous fluoride in the new stannous fluoride/sodium hexametaphosphate dentifrice: an in vitro Live/Dead assay; an in vivo Plaque Glycolysis and Regrowth Model study; a rapid in vitro salivary bacteria metabolic activity study; and a 12-hour in vivo tin-retention study. In the Live/Dead study, the new stannous fluoride/sodium hexametaphosphate dentifrice killed approximately 90% to 99% of the salivary microbes 16 hours after a single exposure. Similarly, the stannous fluoride dentifrice produced statistically significant reductions in plaque acid production and plaque regrowth activity compared to plaque treated with a standard fluoride dentifrice at all time intervals measured after product exposure (15 and 45 minutes). Results from the final two studies collectively demonstrated the presence of total soluble tin, which serves as a marker for the active stannous fluoride, at levels above the minimum concentration for inhibition of salivary bacteria metabolic activity 12 hours posttreatment. These findings confirm the long-lasting antibacterial action of the new stannous fluoride dentifrice, which serves as a basis for its therapeutic benefits.