Background: Eno® (sodium bicarbonate + citric acid, active moiety sodium citrate) is a non-prescription antacid that is used for relief of heartburn, sour stomach, and acid indigestion. Objective: The primary objective of this trial was to determine the time required for regular Eno® to induce a significant acid neutralization effect compared to placebo. Methods: We conducted a randomized, open, crossover study in healthy fasting subjects. Subjects received either regular Eno or placebo (water), with a two-day washout between crossover periods. Changes in gastric pH were measured with a nasogastric pH probe and recorded using a Mark I Gastrograph. Results: Twenty-four subjects completed the study. Eno showed a significant increase in pH within 6 seconds compared to 18 seconds for placebo. Conclusions: Our study suggests that Eno can create a significantly greater and faster neutralization effect when compared to placebo in healthy, fasting individuals. Eno was well tolerated in this study.