The objective of this study was to evaluate the effect of the antireflux barrier formed by Na alginate on pH-metry-defined acid reflux events in preterms. Four times/day, 1 mL/kg of Na alginate was administered as an intervention to the preterm infants whose gastroesophageal reflux disease was confirmed by 24-hour pH monitoring, and the measurement was repeated after 48 hours. The major outcomes were improvement in the number of reflux events per 24 hours, the duration of the longest episode, the number of episodes >5 minutes per 24 hours, and reflux index on pH-metry. Thirty-four (83%) of 41 preterm infants who completed the study had pathologic measurement on 24-hour pH monitoring; 27 (83%) of the patients responded to treatment, whereas 7 patients (17%) did not. Na alginate treatment significantly improved the number of episodes with pH <4 per 24 hours, the reflux index, the number of episodes >5 minutes with pH <4, and the duration of longest episode with pH <4. Patients showed significant improvement in 2 evaluated clinical symptoms, which were vomiting and weight gain after the treatment. No side effect except thickening of stool in 3 patients was observed. Na alginate treatment for gastroesophageal reflux disease in preterm infants seems to be safe and effective.