Objectives: This study assessed the performance of a novel fluoride dentifrice containing micro- fibrillated cellulose (MFC) and 7% silica (Protegera™) versus common fluoride dentifrices. Methods: Removal of extrinsic stains was assessed using the pellicle cleaning ratio (PCR) method, and radioactive dentin abrasivity (RDA) was measured, to calculate a cleaning efficiency index (CEI). Fluoride efficacy was evaluated using widely used remineralization and fluoride uptake methods. Results: The MFC dentifrice removed stained pellicle significantly more effectively than the ADA reference material, Crest Cavity Protection™ and Sensodyne Pronamel™, and had equal performance to three known marketed stain-removing dentifrices (Arm & Hammer™ Advanced Whitening, Crest ProHealth™, and Colgate Optic White™). The MFC dentifrice vehicle had a low RDA (88), which was significantly less than Crest ProHealth (166) and Crest 3D-White™ (183). Based on PCR and RDA data, the CEI was 31% greater for the MFC product than for Crest ProHealth. In a 10-day pH cycling study, the fluoride efficacy of the MFC product was superior to a non-fluoridated control and was not significantly different from Sensodyne Pronamel and Crest Cavity Protection. The MFC dentifrice was superior for promoting fluoride uptake into incipient enamel lesions than the USP reference dentifrice. Conclusion: The low dentin abrasivity MFC dentifrice is highly effective in removing stained pellicle, and is an efficacious fluoride source when compared to other relevant commercially available fluoride dentifrices with high dentin abrasivity. Clinical Significance: Including micro-fibrillated cellulose into a fluoride dentifrice may enhance cleaning performance for the removal of external stain, while lowering abrasivity, and providing an effective fluoride source. This combination of benefits seems well suited to enamel protection and caries prevention.