Purpose: Sodium bicarbonate (NaHCO3) in toothpaste can enhance the removal of biofilms involved in the development of gingivitis. To examine this over an extended time period, this study compared the efficacy and tolerability of twice-daily brushing for 24 weeks with 67% or 0% NaHCO3-containing toothpastes in subjects with moderate gingivitis. Materials and Methods: 247 adults with bleeding after brushing and ≥ 20 gingival bleeding sites were randomized to twice-daily brushing with a 67% NaHCO3 or 0% NaHCO3 toothpaste. The primary efficacy variables were between-treatment differences in number of bleeding sites and the Modified Gingival Index (MGI) score after 24 weeks' use. Secondary efficacy variables included Bleeding Index (BI) and Turesky modification of Quigley-Hein Plaque Index (TPI) (overall and only interproximal sites). Results: The 67% NaHCO3 toothpaste produced statistically significant improvements compared with the 0% NaHCO3 toothpaste in number of bleeding sites (-17.5; 95% CI -20.32, -14.66; p 0.0001) and MGI score (-0.2; 95% CI -0.24, -0.17; p 0.0001) at week 24. These significant differences were also found at 6 and 12 weeks for these measures and at 6, 12, and 24 weeks for BI and TPI scores (including at only interproximal sites) (all p 0.0001). No treatment-related adverse events were reported. Conclusion: Twice-daily brushing with 67% NaHCO3 toothpaste was generally well tolerated and significantly improved indices of gingival bleeding and plaque compared with 0% NaHCO3 toothpaste in subjects with moderate gingivitis. Keywords: biofilm disruption, dental plaque, periodontal disease, sodium bicarbonate, toothpaste