Background & Aims: There is controversy about the efficacy of treating patients with laryngopharyngeal reflux (LPR) using proton pump inhibitors (PPIs). We assessed the effects of high doses of the PPI rabeprazole in patients with LPR. Methods: Patients with LPR symptoms were assigned randomly to receive rabeprazole (20 mg, twice daily, n = 42) or placebo (n = 40) for 12 weeks. All patients completed symptom questionnaires; these provided demographic information and the reflux symptom index before, during, and 6 weeks after cessation of treatment. Videolaryngostroboscopy was used to document the laryngeal findings and determine the reflux finding score. Results: Twenty-four patients (57.1%) in the rabeprazole group and 27 patients (67.5%) in the placebo group had pH-documented LPR. The total reflux symptom index score decreased significantly in the group given rabeprazole, compared with patients given placebo, at weeks 6 and 12, but not at week 18. However, there were no significant differences in reflux finding scores between the rabeprazole and placebo groups at any of the time points. Conclusions: Twelve weeks of treatment with rabeprazole (20 mg, twice daily) significantly improved reflux symptoms, compared with placebo, in patients with LPR. Relapse of symptoms was observed 6 weeks after stopping PPI therapy, indicating the requirement for longer treatment duration in patients with LPR. © 2010 AGA Institute